One Mission, Five Continents: Sharing our Knowledge with the World
The 15th World Congress for Cervical Pathology and Colposcop (IFCPC 2014) will promote the best possible standards of Colposcopy around the world with the goal of guaranteeing that women everywhere receive excellent care. IFCPC will feature structured training sessions that will improve clinician competence, performance and patient outcomes through educational activities focused around the study, prevention, diagnosis, and management of HPV and genital tract diseases. By placing the latest research and techniques at the service of health care professionals on every continent, the congress seeks to bridge the gap between theory and practice.
The BSCCP and 32 National Societies represented by the IFCPC, this congress will provide the perfect forum for sharing international knowledge and experience, dealing with core issues in cervical pathology and colposcopy. Meet the best and brightest minds working in the field at IFCPC 2014.
Actualizaciones sobre las Neoplasias Vulvares Intraepiteliales (VIN) (Revisión)
An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis
M Carolina Reyes, Kumarasen Cooper
Abstract: There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.
Additional Guidance Online for Providers Regarding 9-Valent HPV Vaccine Use Among Persons Who Previously Received HPVVaccination
Additional Guidance Online for Providers Regarding 9-Valent HPV Vaccine Use Among Persons Who Previously Received HPV Vaccination
July 31, 2015 / 64(29);806
A 9-valent human papillomavirus (HPV) vaccine (Gardasil 9, Merck and Co., Inc.) was licensed for use in females and males in the United States in December 2014. This is the third HPV vaccine licensed by the Food and Drug Administration; the other vaccines are the bivalent HPV vaccine, licensed for use in females, and the quadrivalent HPV vaccine, licensed for use in females and males.
In February 2015, the Advisory Committee on Immunization Practices (ACIP) recommended 9-valent HPV vaccine as one of three HPV vaccines that can be used for routine vaccination of females and one of two HPV vaccines for routine vaccination of males. ACIP recommendations were published in a March 2015 report. Additional information has been posted on the CDC website to provide guidance on issues that were not addressed in the March report but are likely to arise during the transition to 9-valent HPV vaccine, including questions about use of 9-valent HPV vaccine among persons who previously received bivalent or quadrivalent HPV vaccine 9vHPV Guidance PDF.
Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer.
Kreimer AR, et al.
Abstract: Purpose Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera. Methods We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression. Results HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative. Conclusion HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.
Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States
Anil K. Chaturvedi⇑, Eric A. Engels, Ruth M. Pfeiffer, Brenda Y. Hernandez, Weihong Xiao, Esther Kim, Bo Jiang, Marc T. Goodman, Maria Sibug-Saber, Wendy Cozen, Lihua Liu, Charles F. Lynch, Nicolas Wentzensen, Richard C. Jordan, Sean Altekruse, William F. Anderson, Philip S. Rosenberg and Maura L. Gillison
Abstract: Purpose Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Patients and Methods: HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. Results: HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020. Conclusion: Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.
Aumenta la incidencia de los tumores de cabeza y cuello causados por VPH
Increase in Head and Neck Cancer in Younger Patients Due to Human Papillomavirus (HPV)
D Young, CC Xiao, B Murphy, M Moore, C Fakhry, TA Day
The face of head and neck cancer has changed dramatically over the past 30 years. There has been a steady decline in the number of tobacco and alcohol related squamous cell carcinomas over the past 30 years, but and increasing incidence of human papillomavirus (HPV) related cancers. Some estimates suggest that 70–90% of new oropharyngeal cancers have evidence of HPV.
Aumento de incidencia de Cáncer de Colon y su conexión con el VPH
Rising Rates of Sporadic Colorectal Cancer in Young Adults: A Possible Environmental by Dr. Monica Malik
The estimated annual incidence of colorectal cancer (CRC) worldwide is 1.3 million, making it the third most common cancer in males and the second most common cancer in females.
There is an increase in CRC incidence in low-income countries and a significantly higher proportion of early-onset cancers.
There is a rising incidence of CRC in young adults from diverse geographic and ethnic backgrounds, which could be linked to environmental pollution or lifestyle factors, such as obesity, physical inactivity, and a diet rich in processed foods.
Possible HPV Connection
Certain oncogenic subtypes of HPV have been conclusively implicated in cancers of the cervix, head and neck, and anal canal. Many investigators have attempted to find an association between HPV and CRC, with discrepant results. Recently, two meta-analyses with data from 16 and 37 studies showed a 10-fold and 6-fold higher risk of CRC with HPV positivity, respectively. More specifically, HPV prevalence varied by geographical region, with the highest prevalence in South America, followed by Asia and the Middle East, suggesting a possible correlation linking high-risk sexual behavior, lifestyle, and HPV infection with CRC rates in resource-constrained countries. Laskar et al.26 detected HPV DNA in 31.2% of patients with RC in their study, of which 76% had HPV subtype 18, 8% had subtype 16, 8% had both subtypes 16 and 18, and 8% had subtypes other than 18 and 16.
CDC recommends only two HPV shots for younger adolescents
For Immediate Release: Wednesday October 19, 2016
CDC today recommended that 11- to 12-year-olds receive two doses of HPV vaccine at least six months apart rather than the previously recommended three doses to protect against cancers caused by human papillomavirus (HPV) infections. Teens and young adults who start the series later, at ages 15 through 26 years, will continue to need three doses of HPV vaccine to protect against cancer-causing HPV infection.
“Safe, effective, and long-lasting protection against HPV cancers with two visits instead of three means more Americans will be protected from cancer,” said CDC Director Tom Frieden, M.D., M.P.H. “This recommendation will make it simpler for parents to get their children protected in time.”
The Advisory Committee on Immunization Practices (ACIP) voted today to recommend a 2-dose HPV vaccine schedule for young adolescents. ACIP is a panel of experts that advises the CDC on vaccine recommendations in the United States. CDC Director Frieden approved the committee’s recommendations shortly after the vote. ACIP recommendations approved by the CDC Director become agency guidelines on the date published in the Morbidity and Mortality Weekly Report (MMWR).
CDC and ACIP made this recommendation after a thorough review of studies over several meetings. CDC and ACIP reviewed data from clinical trials showing two doses of HPV vaccine in younger adolescents (aged 9-14 years) produced an immune response similar or higher than the response in young adults (aged 16-26 years) who received three doses.
Generally, preteens receive HPV vaccine at the same time as whooping cough and meningitis vaccines. Two doses of HPV vaccine given at least six months apart at ages 11 and 12 years will provide safe, effective, and long-lasting protection against HPV cancers. Adolescents ages 13-14 are also able to receive HPV vaccination on the new 2-dose schedule.
CDC will provide guidance to parents, healthcare professionals, and insurers on the change in recommendation. On October 7, 2016, the U.S. Food and Drug Administration (FDA) approved adding a 2-dose schedule for 9-valent HPV vaccine (Gardasil® 9) for adolescents ages 9 through 14 years. CDC encourages clinicians to begin implementing the 2-dose schedule in their practice to protect their preteen patients from HPV cancers.
ACIP, CDC, FDA and partners monitor vaccines in use in the U.S. year-round. These updated recommendations are an example of using the latest available evidence to provide the best possible protection against serious diseases.
Cancers of the anal canal: diagnosis, treatment and future strategies
Cancers of the anal canal: diagnosis, treatment and future strategies
Emma Bown, Vikas Shah, Thiagarajan Sridhar, Kirsten Boyle, David Hemingway, Justin M Yeung
ABSTRACT: Anal cancer is an uncommon cancer; however, it is rising in incidence. There is confusion regarding nomenclature and the distinction between anal canal cancer and anal margin cancer. This article discusses the modern definition, etiology and staging of anal canal and anal margin cancers. Modern chemotherapy and radiotherapy regimens are discussed, in addition to modern imaging and radiotherapy techniques. Future preventative strategies and potential novel treatments are discussed.
Cervical Cancer Screening: Docs Unconvinced on HPV DNA Test
Cervical Cancer Screening: Docs Unconvinced on HPV DNA Test
The US Food and Drug Administration recently approved the use of a human papillomavirus (HPV) test as a primary cervical cancer screening test in women as young as 25 years, yet physicians are unlikely to ditch the Papanicolaou (Pap) test soon, experts say.
Roche's cobas test is 1 of 4 HPV tests on the market, but thus far it is the only one approved for primary screening, rather than for use in conjunction with Pap tests.
The cobas test was initially approved in April 2011 for women aged 21 to 29 years who had an abnormal Pap test and as a "co-test" with the Pap test for women aged 30 to 65 years. The test detects DNA from HPV 16 and HPV 18, the 2 types of HPV that cause 70% of cervical cancer cases worldwide, as well as for DNA from 12 other high-risk types of HPV.
If the cobas test is used as a primary screen, those who test positive for HPV 16 or HPV 18 are supposed to have a colposcopy, according to the FDA. If they test positive for 1 of the other high-risk HPV types, they are supposed to have a Pap test to determine whether they need colposcopy.
"I don't know that we're going to see an immediate change in how patients are screened for cervical cancer," Levi Downs, MD, a spokesman for the Society of Gynecologic Oncology and an associate professor of obstetrics and gynecology at the University of Minnesota School of Medicine, Minneapolis, said to Medscape Medical News.
"We have such a good test now," Dr. Downs said, referring to the Pap test, which physicians first began using in the 1940s. "We know that it has dramatically changed the impact of cervical cancer. Physicians, I think, are going to take their time in deciding what the data (about primary screening with an HPV test) mean."
Despite its approval, critical questions remain unanswered about the HPV test as a primary screening tool for cervical cancer, David Chelmow, MD, chair of obstetrics and gynecology at Virginia Commonwealth University in Richmond, told Medscape Medical News. For example, should women be screened more frequently or less frequently than current guidelines recommend for the Pap test? How should women aged 25 through 29 years be screened, given that the FDA approved cobas as a primary HPV test for those as young as 25 years, but current guidelines advise against routine use of an HPV test in women younger than 30 years? In addition, researchers do not yet know whether primary screening with the cobas test will lead to an increase in colposcopy and cervical biopsies compared with Pap screening.
Characterization of two new monoclonal antibodies against human papillomavirus type 16 L1 protein
Characterization of two new monoclonal antibodies against human papillomavirus type 16 L1 protein
Yan Wang, Qinglong Shang, Weizhen Xu, Di Li, Hongxi Gu and Lanlan Wei
Background: Human papillomavirus type 16 (HPV16) infection is implicated in cervical carcinogenesis. This study aimed to characterize two new monoclonal antibodies (mAbs) against HPV L1 protein. Methods: The immunocompetence of AE3 and AG7 mAbs for HPV L1 protein was evaluated by Western blot analysis, immunostaining, hemagglutination inhibition assay, and ELISA. The heavy chain variable region (VH) and light chain variable region (VL) of AE3 and AG7 mAbs were sequenced and analyzed. Results: Both mAbs specifically recognized HPV16 L1 and virus-like particles (VLPs). Both the affinity and the titer of AE3 mAb were higher than that of AG7. There were differences in sequences in the complementary determining regions (CDR) 2 and 3 of VL, as well as in the CDR1 and CDR3 of VH. The two mAbs have distinct predicted three-dimensional structures. Conclusions: We characterized two mAbs neutralizing antibodies for HPV L1 protein, which would help develop genetic-engineered neutralizing antibodies against HPV16 for diagnostic and therapeutic purposes.
Identification and characterization of small molecule human papillomavirus E6 inhibitors.
Malecka KA, Fera D, Schultz DC, Hodawadekar S, Reichman M, Donover PS, Murphy ME, Marmorstein R
Abstract: Cervical cancer is the sixth most common cancer in women worldwide and the leading cause of women's death in developing countries. Nearly all cervical cancers are associated with infection of the human papillomavirus (HPV). This sexually transmitted pathogen disrupts the cell cycle via two oncoproteins: E6 and E7. Cells respond to E7-mediated degradation of pRB by upregulating the p53 tumor suppressor pathway. However, E6 thwarts this response by binding to the cellular E6-Associating Protein (E6AP) and targeting p53 for degradation. These two virus-facilitated processes pave the way for cellular transformation. Prophylactic HPV vaccines are available, but individuals already infected with HPV lack drug-based therapeutic options. To fill this void, we sought to identify small molecule inhibitors of the E6/E6AP interaction. We designed an ELISA-based high throughput assay to rapidly screen compound libraries and hits were confirmed in several orthogonal biochemical and cell-based assays. Over 88,000 compounds were screened; 30 had in vitro potencies in the mid-nanomolar to mid-micromolar range and were classified as validated hits. Seven of these hits inhibited p53 degradation in cell lines with HPV-integrated genomes. Two compounds of similar scaffold successfully blocked p53 degradation and inhibited cell proliferation in cells stably transfected with E6. Together, these studies suggest that small molecules can successfully block E6-dependent p53 degradation and restore p53 activity. The compounds identified here constitute attractive starting points for further medicinal chemistry efforts and development into beneficial therapeutics.
Maver PJ, Seme K, Korać T, Dimitrov G, Döbrőssy L, Engele L, Iljazović E, Kesić V, Kostova P, Laušević D, Maurina A, Nicula FA, Panayotova Y, Primic Žakelj M,Repše Fokter A, Romejko-Wolniewicz E, Smailytė G, Şuteu O, Świderska-Kiec J, Tachezy R, Valerianova Z, Veerus P, Vīberga I, Znaor A, Zubor P, Poljak M.
Abstract: The burden of cervical cancer in central and eastern Europe is generally higher compared to western or northern Europe due to a history of mostly opportunistic cervical cancer screening practices and due to the strong influence of political and economic changes in post-communist transition. This article describes the current cervical cancer screening practices, organizational plans for the future, and main obstacles that need to be overcome in 16 countries in central and eastern Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and The former Yugoslav Republic of Macedonia. Unfortunately, only a few countries have managed to establish an organized and well-functioning cervical cancer screening program in recent years, whereas most countries in the region are still struggling with implementation-related issues of organized cervical cancer screening. Encouragingly, even in the countries where only opportunistic screening is performed, well-prepared plans and strategies have been established for switching to organized screening in the near future.
Cuidado con los resultados de p16 negativos en CIN-2
HPV Detection and p16INK4a Expression in Cervical Lesions. A Comparative Study
Jordi Genovés, Frances Alameda, Gemma Mancebo, Josep Maria Solé,
Abstract: p16INK4a expression in dysplastic cervical lesions is related to high-risk human papillomavirus (HR-HPV) infection. The immunohistochemical expression of this protein in these lesions allows an increase in diagnostic reproducibility in biopsies and the introduction of prognostic factors in low-grade lesions. Here, we studied the immunohistochemical expression of p16 in 86 dysplastic cervical lesions, 54 cervical intraepithelial neoplasms - grade 1 (CIN-I), 23 CIN-II, and 9 CIN-III. In addition, we performed HPV detection and genotyping. We detected HR-HPV in 19/54 CIN-I, 21/23 CIN-II and 9/9 CIN-III cases. p16 INK4a immunoreactivity was observed in 7/19 CIN-I HR-HPV–positive, 17/21 CIN-II HR-HPV–positive and all CIN-III cases. Immunoreactivity for p16 INK4a was found in 7/54 CIN-I and in 17/23 CIN-II cases. In the follow-up, we detected 3 p16-positive high-grade squamous epithelial lesions (HSIL: CIN-II and CIN-III) in the CIN-I/p16-negative group and 5 p16-positive HSIL cases in the CIN-II/p16-negative group. We conclude that p16 negativity in CIN-I and CIN-II biopsies does not always imply regression of the lesion and that the diagnosis of CIN-II should not be based solely on p16 results.
Current status of human papillomavirus vaccination
Current status of human papillomavirus vaccination
Brotherton, Julia M.L.; Ogilvie, Gina S.
Abstract: Purpose of review: In this article, we review the impact of the quadrivalent and bivalent prophylactic human papillomavirus (HPV) vaccines on HPV infection and disease, review alternative vaccine dosing schedules, the vaccination of men and the nine-valent HPV vaccine. Recent findings: HPV vaccines have had dramatic impacts on the prevalence of targeted HPV types (6,11,16 and 18), genital warts and precancerous cervical lesions. Population coverage would be facilitated by adopting two-dose schedules, with recent findings that two-dose schedules in young adolescents are as immunogenic as three doses in young adults. Extension of vaccination to men, particularly for men who have sex with men, could further reduce population prevalence of HPV and provide direct protection to men against genital warts and anal, penile and oropharyngeal cancers. The nine-valent HPV vaccine has demonstrated equivalent protection against the four types in the quadrivalent vaccine and high efficacy against the next five commonest causes of cervical cancer (HPV types 31,33,45,52 and 58). If cost-effective, it may extend the spectrum of protection against cervical cancer available through vaccination. Summary: HPV vaccination is an effective strategy for reducing the burden of HPV-related disease. New schedules, target populations and vaccines promise to expand this potential further.
Detection of Human Papillomavirus in Non-Small Cell Carcinoma of the Lung
Detection of Human Papillomavirus in Non-Small Cell Carcinoma of the Lung
Sing Yun Chang, Michael Keeney, Mark Law, Janis Donovan, Marie-Christine Aubry, Joaquin Garcia
Abstract: High-risk human papillomavirus (hrHPV) is an etiologic agent in squamous cell carcinoma (SqCC) arising in the oropharynx and cervix, and a proven prognostic factor in oropharyngeal SqCC. Many studies have found HPV in non-small cell lung carcinoma (NSCLC). Recent studies advocate the detection of mRNA transcripts of E6/E7 as more reliable evidence of transcriptively active HPV in tumor cells. The clinical significance of finding HPV remains unclear in NSCLC. This study sought to determine the prevalence of biologically active HPV infection in NSCLC comparing different methodologies. Surgical pathology material from resected primary lung adenocarcinoma (ADC; n = 100) and SqCC (n = 96) were retrieved to construct tissue microarrays. In-situ hybridization (ISH) for hrHPV DNA (DNA-ISH), hrHPV E6/E7 RNA (RNA-ISH), and p16 immunohistochemistry (IHC) were performed. Cases of oropharyngeal SqCC with known HPV infection were used as positive controls. Expression of p16 was scored as positive if at least 70% of tumor cells showed diffuse and strong nuclear and cytoplasmic staining. Punctate nuclear hybridization signals by DNA-ISH in the malignant cells defined an HPV-positive carcinoma. Of the 196 patients (range 33-87 years; 108 men), p16 was positive in 19 ADC and 9 SqCC, but HPV DNA-ISH and RNA-ISH were negative in all cases. Our study did not detect HPV infection by DNA-ISH or RNA-ISH in any cases of primary NSCLC despite positive p16 expression in a portion of ADC and SqCC. p16 should therefore not be used as a surrogate marker for HPV infection in NSCLC.
"En el nuevo estudio, los investigadores compararon las respuestas inmunitarias de 830 personas divididas en tres grupos: las niñas de 9 a 13 años que recibieron dos dosis de la vacuna contra el VPH separados seis meses, las niñas de la misma edad que recibieron tres dosis durante seis meses, y las mujeres entre 16 y 26 años que recibieron tres dosis de más de seis meses. Todos los participantes recibieron la vacuna Gardasil, que protege contra cuatro cepas del virus."
"Si dos dosis en niñas generan el mismo tipo de respuesta inmune en tres dosis en las mujeres, se puede inferir que las niñas podrían ser protegidos de la enfermedad, incluso si usted no mide resultados de la enfermedad en las niñas", dijo Kahn.
"Un mes después de la última inyección contra el VPH , las niñas que recibieron dos dosis de la vacuna tenían aproximadamente la misma respuesta inmune como las niñas que recibieron tres dosis."
"Sin embargo, dos o tres años después de la vacunación, las niñas que recibieron dos dosis tuvieron una respuesta inmune reducida a las cepas VPH 18 y 6 en comparación con los que recibieron tres dosis."
El trabajo está publicado en JAMA el 30 de abril de 2013
*Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women. A Randomized Clinical Trial*
Simon R. M. Dobson; Shelly McNeil; Marc Dionne; Meena Dawar; Gina Ogilvie; Mel Krajden; Chantal Sauvageau; David W. Scheifele; Tobias R. Kollmann; Scott A. Halperin; Joanne M. Langley; Julie A. Bettinger; Joel Singer; Deborah Money; Dianne Miller; Monika Naus, MD; Fawziah Marra; Eric Young.
Importance: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.
Objective: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.
Design, Setting, and Patients: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).
Intervention: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.
Main Outcomes and Measures: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.
Results: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36.
Conclusions and Relevance: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.
ETSs en números
Incidence, Prevalence, and Cost of Sexually Transmitted Infections in the United States
CDC’s estimates of sexually transmitted infections in United States, 2008:
Annual new infections - (Incidence) 20 million
Total infections (Prevalence) 110 million
Total medical costs $16 billion
In February 2013, CDC published two analyses that provide an in-depth look at the severe human and economic burden of sexually transmitted infections (STIs) in the United States.
CDC’s new estimates show that there are about 20 million new infections in the United States each year, costing the American healthcare system
nearly $16 billion in direct medical costs alone.
America’s youth shoulder a substantial burden of these infections. CDC estimates that half of all new STIs in the country occur among young men and women. In addition, CDC published an overall estimate of the number of prevalent STIs in the nation. Prevalence is the total number of new and existing infections at a given time. CDC’s new data suggest that there are more than 110 million total STIs among men and women across the nation.
CDC’s analyses included eight common STIs: chlamydia, gonorrhea,
hepatitis B virus (HBV), herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV), human papillomavirus (HPV), syphilis, and trichomoniasis.
Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials
Guglielmo Ronco, Joakim Dillner, K Miriam Elfström, Sara Tunesi, Peter J F Snijders, Marc Arbyn, Henry Kitchener, Nereo Segnan, Clare Gilham, Paolo Giorgi-Rossi, Johannes Berkhof, Julian Peto, Chris J L M Meijer. The International HPV screening working group†
Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176.464 women aged 20—64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40—0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46—1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25—0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15—0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1—12·1) and 8·7 per 105 (3·3—18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9—27·0) and 36·0 per 105 (23·2—53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14—0·69) than for squamous-cell carcinoma (0·78, 0·49—1·25). The rate ratio was lowest in women aged 30—34 years (0·36, 0·14—0·94). Interpretation: HPV-based screening provides 60—70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.
Gardasil 9 Vaccine Protects against Additional HPV Types
In a large randomized clinical trial, a new human papillomavirus (HPV) vaccine effectively prevented infection and disease caused by nine high-risk HPV types, including seven types that cause cervical and other cancers—five of which were not covered by the previously available HPV vaccines—and two types that cause genital warts.
New England Journal of Medicine, February 18, 2015 (See the abstract.)
Gardasil 9 Vaccine Protects against Additional HPV Types
Gardasil 9 Vaccine Protects against Additional HPV Types
Summary: In a large randomized clinical trial, a new human papillomavirus (HPV) vaccine effectively prevented infection and disease caused by nine high-risk HPV types, including seven types that cause cervical and other cancers—five of which were not covered by the previously available HPV vaccines—and two types that cause genital warts.
A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women
Elmar A. Joura, Anna R. Giuliano, Ole-Erik Iversen, Celine Bouchard, Constance Mao, Jesper Mehlsen, Edson D. Moreira, Jr., Yuen Ngan, Lone Kjeld Petersen, Eduardo Lazcano-Ponce, Punnee Pitisuttithum, Jaime Alberto Restrepo, Gavin Stuart, Linn Woelber, Yuh Cheng Yang, Jack Cuzick, Suzanne M. Garland, Warner Huh, Susanne K. Kjaer, Oliver M. Bautista, Ivan S.F. Chan, Joshua Chen, Richard Gesser, Erin Moeller, Michael Ritter, Scott Vuocolo, and Alain Luxembourg, for the Broad Spectrum HPV Vaccine Study
Abstract: Background. The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. Methods. We performed a randomized, international, double-blind, phase 2b–3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. Results. The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. Conclusions. The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).
Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain
Benjamín García-Espinosa, Ernesto Moro-Rodríguez and Emilio Álvarez-Fernández
Abstract: Background. Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. Methods: A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. Results: We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). Conclusion: As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited.
Fuente: J. Ernesto Moro (@EMoroRodriguez) twitteó a las 2:53 PM on mié, nov 28, 2012: #bmccancer Genotype distribution of HPV in histological sections in CIN and invasive cervical ca. in Madrid, Spain http://t.co/McFFKvnj
HPV 2015 - Lisboa
Join us for the 30th International Papillomavirus Conference & Clinical and Public Health Workshops (HPV 2015) that will be held September 17-21 in Lisbon, Portugal. This year we will focus on HPV and Globalization, exploring new worlds in research as well as new proposals to reduce inequities in global health.
HPV gathers researchers, clinicians and other health professionals to share and exchange research regarding the epidemiology of HPV, virus vaccines, cervical cancer prevention and other papillomavirus associated diseases. We host an international forum that enables the exchange of knowledge between the research and clinical communities showcasing the latest advances in science and practice through state of the art oral and poster presentations.
HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand.
HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand.
Siriaunkgul S, Settakorn J, Sukpan K, Srisomboon J, Utaipat U, Lekawanvijit S, Khunamornpong S.
Abstract: Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age 57.9±13.2 years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand.
In a new study, researchers have confirmed that infection with human papillomavirus (HPV) 16 precedes the development of some head and neck cancers. Previous studies have established an association between HPV-16 infection and oropharyngeal cancer, a type of head and neck cancer. The new study is the first to do so using samples collected from participants prior to their cancer diagnoses.
The study also reported, for the first time, an association between head and neck cancer risk and infection with HPV types other than HPV 16.
Ilir Agalliu, M.D., Sc.D., and Robert D. Burk, M.D., of Albert Einstein College of Medicine in New York, and their colleagues reported the results of this prospective study January 21 in JAMA Oncology.
Human papillomavirus-associated oral intraepithelial neoplasia.
Woo SB, Cashman EC, Lerman MA
Abtract: This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer. Modern Pathology advance online publication, 19 April 2013; doi:10.1038/modpathol.2013.70.
Human papillomavirus–associated adenocarcinoma of the base of the tongue
John Hanna, Julie D.R. Reimann, Robert I. Haddad, Jeffrey F. Krane
Summary: Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinoma with characteristic clinical and pathologic features relative to their non–HPV–associated counterparts. Here we describe 2 cases of HPV-associated adenocarcinoma of the oropharynx. Both cases arose at the base of the tongue, and neither had the histologic or immunohistochemical features of a primary salivary gland tumor or metastasis from another location. One patient had metastases to neck lymph nodes and the lungs and died of disease 37 months after diagnosis. Evidence for an HPV association consisted of strong diffuse expression of p16, polymerase chain reaction–based detection of HPV16 DNA sequences, and localization of HPV by in situ hybridization within tumor cells of both primary and metastatic lesions. These results further expand the spectrum of HPV-associated head and neck malignancy. This rare entity should be distinguished from primary salivary gland adenocarcinoma and may be a candidate for HPV-specific targeted therapies.
Human Papillomavirus Prevalence in Invasive Anal Cancers in the United States Before Vaccine Introduction.
[J Low Genit Tract Dis. 2013]
Steinau M, Unger ER, Hernandez BY, Goodman MT, Copeland G, Hopenhayn C, Cozen W, Saber MS, Huang Y, Peters ES, Lynch CF, Wilkinson EJ, Rajeevan MS, Lyu C, Saraiya M.
Abstract. OBJECTIVE: This study aimed to conduct a representative survey of human papillomavirus (HPV) prevalence and its genotype distribution in invasive anal cancer specimens in the United States. MATERIALS AND METHODS: Population-based archival anal cancer specimens were identified from Florida, Kentucky, Louisiana, and Michigan cancer registries and Surveillance, Epidemiology, and End Results (SEER) tissue repositories in Hawaii, Iowa, and Los Angeles. Sections from 1 representative block per case were used for DNA extraction. All extracts were assayed first by linear array and retested with INNO-LiPA if inadequate or HPV negative. RESULTS: Among 146 unique invasive anal cancer cases, 93 (63.7%) were from women, and 53 (36.3%) were from men. Human papillomavirus (any type) was detected in 133 cases (91.1%) and 129 (88.4%) contained at least 1 high risk-type, most (80.1%) as a single genotype. Human papillomavirus type 16 had the highest prevalence (113 cases, 77.4%); HPV types 6, 11, 18, and 33 were also found multiple times. Among HPV-16-positive cases, 37% were identified as prototype variant Ep, and 63% were nonprototypes: 33% Em, 12% E-G131G, 5% Af1, 4% AA/NA-1, 3% E-C109G, 3% E-G131T, 2% As, and 1% Af2. No significant differences in the distributions of HPV (any), high-risk types, or HPV-16/18 were seen between sex, race, or age group. CONCLUSIONS: The establishment of prevaccine HPV prevalence in the United States is critical to the surveillance of vaccine efficacy. Almost 80% of anal cancers were positive for the vaccine types HPV-16 or HPV-18, and in 70%, these were the only types detected, suggesting that a high proportion might be preventable by current vaccines.
Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain.
Benjamín García-Espinosa, Ernesto Moro-Rodríguez and Emilio Álvarez-Fernández
Background: We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). Methods: We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. Results: We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). Conclusion: The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma.
Examining the Association between Oral Health and Oral HPV Infection
Thanh Cong Bui, Christine M. Markham, Michael Wallis Ross, Patricia Dolan Mullen
Abstract: Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009–2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25–1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13–2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07–1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15–2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.
What are human papillomaviruses?
Which cancers are caused by HPV?
Who gets HPV infections?
Can HPV infections be prevented?
What HPV vaccines are available?
How do HPV vaccines work?
How effective are HPV vaccines?
Why are these vaccines important?
Why is it important for more people to be vaccinated?
How safe are the HPV vaccines?
Who should get the HPV vaccines?
Should the vaccines be given to people who are already infected with HPV?
Should women who already have cervical cell changes get the vaccines?
Do women who have been vaccinated still need to be screened for cervical cancer?
How much do these vaccines cost, and will insurance pay for it?
What research is being done on strategies to prevent HPV infection?
How can people learn more about HPV infection?
Human papillomavirus-associated oral intraepithelial neoplasia: Modern Pathology
Human papillomavirus-associated oral intraepithelial neoplasia.
Sook-Bin Woo, Emma C Cashman and Mark A Lerman
Abstact: This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term ‘HPV-associated Oral Intraepithelial Neoplasia’ to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer.
I Encuentro Sudamericano del Virus Papiloma Humano
Estimados colegas y amigos:
Este es un momento importante en el campo de la investigación del Papiloma Virus Humano, cuyos resultados están traduciéndose herramientas el alto impacto en la salud pública; sin embargo, la incorporación de estos avances ha sido muy lenta en algunos de los países de nuestra Región.
Creemos que este I Encuentro Sudamericano del Virus Papiloma Humano, propiciará un necesario intercambio de nuevos conocimientos, experiencias y debate sobre el estado de la investigación del VPH, en nuestra región y las dificultades para implementar las necesarias innovaciones en este campo. La discusión sobre el impacto de las estrategias actuales de prevención y control del VPH, en nuestros países del cono sur, estimulará nuevas colaboraciones y fortalecerá las ya existentes.
I Encuentro Sudamericano del Virus Papiloma Humano, ofrecerá un programa científico dinámico, potenciando la interacción de profesionales desde la perspectiva de la clínica (Ginecología y Obstetricia, Infectología, Microbiología, Dermatología y Venereología, Oncología, Enfermedades Respiratorias, Patología), de la Epidemiología, Salud Pública, Economía de la Salud, hasta de las ciencias básicas (Biología, Genética).
Espero recibirlos, en Marzo de 2014 en Santiago de Chile y que puedan disfrutar de la belleza y hospitalidad que Chile les ofrece!.
Immune-Based Treatment Shows Promise against Metastatic Cervical Cancer
April 16, 2015 by NCI Staff
Dr. Christian Hinrichs and Susan Scott, who participated in the NCI immunotherapy trial, at a follow-up visit. Ms. Scott had a complete response to the treatment that is still ongoing after 24 months. (Photo courtesy of Susan Scott)
Two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer (ACT). A third patient experienced a reduction in tumor size for a short time following the treatment.
The findings, from an early-phase clinical trial conducted by researchers from NCI’s Center for Cancer Research (CCR), were published March 30 in the Journal of Clinical Oncology (JCO).
The treatment tested in the trial consisted of an infusion of immune cells—know as tumor-infiltrating lymphocytes (TILs)—that were collected from each patient’s own tumor and expanded in the laboratory. ACT has had success in small clinical trials of patients with melanoma and some blood cancers conducted by researchers at NCI and several other institutions.
But this is the first time ACT has been tested in patients with cervical cancer, explained the study’s lead author, Christian Hinrichs, M.D., of CCR’s Surgery Branch.
Nearly all cervical cancers are caused by persistent infections with certain types of the human papillomavirus (HPV). HPV-infected cells produce specific proteins, or antigens—known as E6 and E7—that can be recognized by T cells, which are immune cells that play a critical role in the body’s response to infectious agents and infected cells. All of the patients in the trial had tumors that express the E6 and E7 proteins.
The researchers selected for expansion those T cells that would have the greatest likelihood of attacking cancer cells. They did this chiefly by identifying those that were most reactive for the E6 and E7 proteins, although other characteristics were also considered. Patients received chemotherapy before infusion of the expanded T cells and regular infusions with IL-2 for up to three days afterward, both of which have been shown to enhance T cells’ ability to eradicate cancer cells.
The findings published in JCO cover the nine patients in the trial with cervical cancer. The trial also includes patients with other HPV-related cancers, including oropharyngeal and anal cancer.
The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response lasted for 3 months. The three patients whose tumors responded to treatment had T cells that were reactive to the HPV proteins. They also had reactive T cells in samples of blood collected one month after treatment. There were no apparent side effects related to the cell infusion, the researchers reported, although most patients experienced side effects from the pre-infusion chemotherapy and post-infusion IL-2 treatments.
“There’s been a lot of hope that’s come from seeing the complete, long-lasting tumor responses in cellular therapy for melanoma and B-cell cancers,” Dr. Hinrichs said. “For the first time, we’re seeing that sort of response in an epithelial cancer.”
Despite coming from a trial with such a small number of patients, “these results are impressive and suggest that this highly personalized therapeutic modality warrants further investigation,” wrote Kunle Odunsi, M.D., Ph.D., of the Roswell Park Cancer Institute, and his colleagues in an accompanying editorial in JCO.
Based on these early results, the trial protocol has been amended so that only patients whose TILs are reactive for the E6 and E7 proteins will receive the treatment. “This way we can only treat the patients with the highest likelihood of responding to the treatment,” Dr. Hinrichs said.
Another trial testing a different form of ACT in patients with HPV-related cancers has been opened at NCI, Dr. Hinrichs added. That trial involves genetically engineering T cells collected from patients’ blood (rather than their tumors) to express a receptor that’s specific for the E6 and E7 proteins.
Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus–Targeted Tumor-Infiltrating T Cells
Sanja Stevanović, Lindsey M. Draper, Michelle M. Langhan, Tracy E. Campbell, Mei Li Kwong, John R. Wunderlich, Mark E. Dudley, James C. Yang, Richard M. Sherry, Udai S. Kammula, Nicholas P. Restifo, Steven A. Rosenberg, and Christian S. Hinrichs
Purpose: Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. Patients and Methods: Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. Results: Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). Conclusion: Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted.
FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV.
Comunicado: La Administración de Alimentos y Medicamentos de los Estados Unidos (FDA por su siglas en inglés) aprobó hoy Gardasil 9 (Vacuna nanovalente recombinante para el virus del papiloma humano) para la prevención de ciertas enfermedades causadas por nueve tipos de virus del papiloma humano (VPH). Gardasil 9 protege contra nueve tipos de VPH, cinco tipos más de VPH que Gardasil (previamente aprobada por la FDA), y tiene el potencial de prevenir aproximadamente el 90 por ciento del cáncer del cuello uterino, de la vulva, vaginal y anal.
Gardasil 9 es una vacuna aprobada para su uso en mujeres entre las edades de 9 a 26 años y en hombres de entre 9 a 15 años. Está aprobada para la prevención del cáncer de cérvix, de la vulva, vaginal y anal causado por los tipos de VPH 16, 18, 31, 33, 45, 52 y 58, y para la prevención de las verrugas genitales causadas por los tipos de VPH 6 o 11. Gardasil 9 añade protección contra cinco tipos adicionales de VPH-31, 33, 45, 52 y 58- los que causan aproximadamente el 20 por ciento del cáncer de cuello uterino y no están cubiertos por vacunas contra el VPH previamente aprobadas por la FDA.
"La vacunación es una medida de salud pública de importancia crítica para reducir el riesgo de la mayoría de los cánceres del cuello uterino, genital y anal causados por el VPH", dijo la doctora Karen Midthun, MD, directora del Centro para la Evaluación e Investigación de Productos Biológicos de la FDA. "La aprobación de Gardasil 9 proporciona una mayor protección contra los cánceres relacionados al VPH”.
Se realizó un estudio aleatorizado, clínico controlado en los EE.UU. y a nivel internacional en aproximadamente 14,000 mujeres de entre 16 a 26 años que obtuvieron resultados negativos para los tipos de VPH que cubre la vacuna al inicio del estudio. Los participantes del estudio recibieron Gardasil o Gardasil 9. Se determinó que Gardasil 9 fue 97 por ciento efectiva en la prevención de cáncer de cuello uterino, de la vulva y vaginal causados por los cinco tipos adicionales de VPH (31, 33, 45, 52, y 58). Además, Gardasil 9 es tan eficaz como Gardasil para la prevención de enfermedades causadas por los cuatro tipos de VPH compartidos (6, 11, 16, y 18), basado en las respuestas de anticuerpos similares en participantes en los estudios clínicos.
Debido a la baja incidencia de cáncer anal causada por los cinco tipos de VPH adicionales, la prevención del cáncer anal se basa en la demostraron efectividad del 78 por ciento de Gardasil y datos adicionales sobre anticuerpos en los hombres y mujeres que recibieron Gardasil 9.
La eficacia de Gardasil 9 en mujeres y hombres de entre 9 a 15 años se determinó en estudios que midieron las respuestas de anticuerpos a la vacuna en aproximadamente 1,200 hombres y 2,800 mujeres en este grupo de edad. Las respuestas a los anticuerpos fueron similares a los de las mujeres 16 a 26 años de edad. Con base en estos resultados, se espera que la vacuna tenga una eficacia similar cuando se utiliza en este grupo de edad más joven.
Gardasil 9 se administra en tres inyecciones separadas, con la dosis inicial seguida de inyecciones adicionales que se administran posteriormente a los dos y seis meses. En base a todas las indicaciones de uso aprobadas por la FDA, el beneficio potencial completo de Gardasil 9 lo obtienen aquellos que son vacunados antes de contraer la infección con las cepas de VPH cubiertas por la vacuna.
La seguridad de Gardasil 9 fue evaluada en aproximadamente 13,000 hombres y mujeres. Las reacciones adversas más frecuentes fueron dolor en el sitio de la inyección, hinchazón, enrojecimiento y dolor de cabeza.
Gardasil 9 es fabricado por Merck Sharp & Dohme Corp., una subsidiaria de Merck & Co., Inc., con sede en Whitehouse Station, Nueva Jersey.
Ninguna mujer deberia morir por el cáncer de cuello uterino
January Is Cervical Cancer Awareness Month
The most important thing you can do to help prevent cervical cancer is to get screened regularly starting at age 21.
Cervical cancer is highly preventable with regular screening tests and appropriate follow-up care. It also can be cured when found early and treated. Cervical cancer is almost always caused by the human papillomavirus (HPV). Vaccines are available to protect against the types of HPV that most often cause cervical cancer.
Novedades sobre el Ca de cervix y ERB2; carta en Nature
Landscape of genomic alterations in cervical carcinomas
Akinyemi I. Ojesina, Lee Lichtenstein, Samuel S. Freeman, et al.
Cervical cancer is responsible for 10–15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma–normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour–normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.
Un nuevo estudio ha revelado marcadas diferencias en el terreno genómica de los dos tipos más comunes de cáncer de cuello uterino, lo que sugiere que los pacientes que podrían beneficiarse de terapias moleculares dirigidas a la idiosincrasia de cada tipo.
El estudio, publicado el 23 de agosto 2013 en la versión online de la revista Cancer realizado por investigadores del Instituto del Cáncer Dana-Farber y el Hospital Brigham y de Mujeres (BWH), es el primero en comparar el espectro de mutaciones genéticas relacionadas con el cáncer en los dos principales subtipos de cáncer de cuello uterino - adenocarcinoma y carcinoma de células escamosas. En pruebas con 80 muestras de tumores de cuello uterino, los investigadores encontraron altas tasas de mutaciones en dos genes: PIK3CA y KRAS. Aunque las mutaciones PIK3CA aparecieron en ambos subtipos, se encontraron mutaciones de KRAS sólo en adenocarcinomas.
Oncogenic mutations in cervical cancer
Wright, A. A., Howitt, B. E., Myers, A. P., Dahlberg, S. E., Palescandolo, E., Van Hummelen, P., MacConaill, L. E., Shoni, M., Wagle, N., Jones, R. T., Quick, C. M., Laury, A., Katz, I. T., Hahn, W. C., Matulonis, U. A. and Hirsch, M. S.
Human Papillomavirus Prevalence in Invasive Anal Cancers in the United States Before Vaccine Introduction
Steinau, Martin; Unger, Elizabeth R.; Hernandez, Brenda Y. ; Goodman, Marc T.; Copeland, Glenn; Hopenhayn, Claudia; Cozen, Wendy; Saber, Maria S.; Huang, Youjie; Peters, Edward S.; Lynch, Charles F.; Wilkinson, Edward J.; Rajeevan, Mangalathu S.; Lyu, Christopher; Saraiya, Mona
Abstract: Objective: This study aimed to conduct a representative survey of human papillomavirus (HPV) prevalence and its genotype distribution in invasive anal cancer specimens in the United States. Materials and Methods: Population-based archival anal cancer specimens were identified from Florida, Kentucky, Louisiana, and Michigan cancer registries and Surveillance, Epidemiology, and End Results (SEER) tissue repositories in Hawaii, Iowa, and Los Angeles. Sections from 1 representative block per case were used for DNA extraction. All extracts were assayed first by linear array and retested with INNO-LiPA if inadequate or HPV negative. Results: Among 146 unique invasive anal cancer cases, 93 (63.7%) were from women, and 53 (36.3%) were from men. Human papillomavirus (any type) was detected in 133 cases (91.1%) and 129 (88.4%) contained at least 1 high risk-type, most (80.1%) as a single genotype. Human papillomavirus type 16 had the highest prevalence (113 cases, 77.4%); HPV types 6, 11, 18, and 33 were also found multiple times. Among HPV-16–positive cases, 37% were identified as prototype variant Ep, and 63% were nonprototypes: 33% Em, 12% E-G131G, 5% Af1, 4% AA/NA-1, 3% E-C109G, 3% E-G131T, 2% As, and 1% Af2. No significant differences in the distributions of HPV (any), high-risk types, or HPV-16/18 were seen between sex, race, or age group. Conclusions: The establishment of prevaccine HPV prevalence in the United States is critical to the surveillance of vaccine efficacy. Almost 80% of anal cancers were positive for the vaccine types HPV-16 or HPV-18, and in 70%, these were the only types detected, suggesting that a high proportion might be preventable by current vaccines.
Una nueva arma en la lucha contra el cáncer del cuello uterino.
An RNA Aptamer Provides a Novel Approach for the Induction of Apoptosis by Targeting the HPV16 E7 Oncoprotein
Clare Nicol, Özlem Cesur, Sophie Forrest, Tamara A. Belyaeva, David H. J. Bunka, G. Eric Blair, Nicola J. Stonehouse
Abstract. Background: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, which is a major causative agent of cervical cancer. Cellular transformation is associated with deregulated expression of the E6 and E7 oncogenes. E7 has been shown to bind a number of cellular proteins, including the cell cycle control protein pRb. In this study, RNA aptamers (small, single-stranded oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed as molecular tools to further investigate these protein-protein interactions. Methodology/Principal Findings: This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining). GST-pull down and bead binding assays were used to demonstrate that the binding of A2 required N-terminal residues of E7 known to be involved in interaction with the cell cycle control protein, pRb. Using a similar approach, A2 was shown to disrupt the interaction between E7 and pRb in vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels, as observed by immunoblotting. Conclusions/Significance: This paper includes the first characterisation of the effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis. Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials. In addition to its role as a molecular tool, A2 could have further applications in the future.
Lee SH. Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil® vaccination—A case report Advances in Bioscience and Biotechnology 2012, 3, 1214-1224. doi: 10.4236/abb.2012.38148. DOI: 10.4236/abb.2012.38148
ABSTRACT: A same-nested PCR was used to re-amplify the amplicon of a hypervariable region of the HPV-16 L1 gene DNA in the postmortem blood and splenic tissue obtained at autopsy of a formerly healthy teenage girl who suffered a sudden unexpected death in sleep 6 months after 3 intramuscular injections of a quadrivalent HPV vaccine, Gardasil®. A full autopsy analysis revealed no cause of death. The HPV-16 gene DNA detected in the postmortem materials was similar to the HPV-16 gene DNA fragments in Gardasil® in that both were in non-B-conformation, requiring nondegenerate GP6 and MY11 primers to re-amplify the PCR amplicon for detection and to generate a template useful for direct DNA sequencing. A sequence excised from the base-calling DNA sequencing electropherogram was analyzed by Basic Local Alignment Search Tool (BLAST) alignment and a 45 - 60 base sequence fully matched with a standard hypervariable region of the HPV-16 L1 gene retrieved from the National Center for Biotechnology Information database validated the correct genotyping for HPV- 16 L1 gene DNA. These naked non-proliferating HPV- 16 L1 gene DNA fragments appeared to be in the macrophages of the postmortem blood and spleen, and were protected from degradation by binding firmly to the particulate aluminum adjuvant used in vaccine formulation. The significance of these HPV DNA fragments of a vaccine origin found in post-mortem materials is not clear and warrants further investigation.
Complete genome sequences of three novel human papillomavirus types, 175, 178, and 180.
Johansson H, Forslund O
Abstract: We report the characterization of three novel human papillomavirus (HPV) types of the genus Gammapapillomavirus. HPV175 and HPV180 were isolated from a condyloma. HPV178 was isolated from healthy skin adjacent to an actinic keratosis.
HIV Infection Alters the Spectrum of HPV Subtypes Found in Cervical Smears and Carcinomas from Kenyan Women
Innocent O. Maranga, Lynne Hampson, Anthony W. Oliver, Xiaotong He, Peter Gichangi, Farzana Rana, Anselmy Opiyo and Ian N. Hampson
Infection with high risk HPV is implicated in pre-cancerous squamous intraepithelial lesions and their progression to cervical cancer. In the developed countries, infection with HPV 16 and 18 accounts for ~70% of cervical cancers, but it has been established that HPV type prevalence differs according to worldwide geographical location. In sub Saharan Africa infection with HPV is known to be augmented by HIV, which is endemic in this region. It is not yet clear, however, whether this ultimately influences progression to cervical cancer. PapillocheckTM and multiplex PCR were used to determine the range of HPV genotypes found in cervical smears and carcinomas from HIV positive and negative Kenyan women. Smear samples from HIV-positive women had a higher prevalence of: multiple HPV infections; high-risk HPVs 52, 58, 68, potential high risk 53/70, low-risk 44/55 and abnormal cytology compared to HIV-negative women. A low overall prevalence (~8%) of types 16/18 was found in all smear samples tested (n = 224) although this increased in invasive cervical carcinoma tissues to ~80% for HIV-negative and ~46% for HIV-positive women. Furthermore, HPV45 was more common in cervical carcinoma tissues from HIV-positive women.
In summary HIV infection appears to alter the spectrum of HPV types found in both cervical smears and invasive cervical carcinomas. It is hypothesised there could be a complex interplay between these viruses which could either positively or negatively influence the rate of progression to cervical cancer.
Recommend the HPV vaccine series the same way you recommend the other adolescent vaccines. For example, you can say "Your child needs these shots today," and name the all of the vaccines recommended for the child’s age.
"Parents may be interested in vaccinating, yet still have questions. Taking the time to listen to parents’ questions helps you save time and give an effective response. CDC research shows these straightforward messages work with parents when discussing HPV vaccine—and are easy for you or your staff to deliver."
The "HPV vaccine is cancer prevention" message resonates strongly with parents. In addition, studies show that a strong recommendation from you is the single best predictor of vaccination.
"HPV vaccine is very important because it prevents cancer. I want your child to be protected from cancer, and I know you want that too. That's why I'm recommending that your daughter/son receive the first dose of HPV vaccine today."
Disease prevalence is not understood, and parents are unclear about what the vaccine actually protects against.
"HPV can cause cancers of the cervix, vagina and vulva in women, cancer of the penis in men, and cancers of the anus and the mouth or throat in both women and men. There are about 26,000 of these cancers each year—and most could be prevented with HPV vaccine. There are also many more precancerous conditions requiring treatment that can have lasting effects."
Parents want a concrete reason why 11-12 year olds should receive HPV vaccine.
"We're vaccinating today so your child will have the best protection possible long before the start of any kind of sexual activity. We vaccinate people well before they are exposed to an infection, as is the case with measles and the other recommended childhood vaccines. Similarly, we want to vaccinate children well before they get exposed to HPV."
Parents may be concerned that vaccinating may be perceived by the child as permission to have sex.
"Research has shown that getting the HPV vaccine does not make kids more likely to be sexually active or start having sex a younger age."
Parents might believe their child won't be exposed to HPV because they aren't sexually active or may not be for a long time.
"HPV is so common that almost everyone will be infected at some point. It is estimated that 79 million Americans are currently infected with 14 million new HPV infections each year. Most people infected will never know. Even if your son/daughter waits until marriage to have sex, or only has one partner in the future, he/she could still be exposed."
Emphasizing your personal belief in the importance of HPV vaccine helps parents feel secure in their decision.
"I strongly believe in the importance of this cancer-preventing vaccine, and I have given HPV vaccine to my son/daughter/grandchild/niece/nephew/friend's children. Experts (like the American Academy of Pediatrics, cancer doctors, and the CDC) also agree that this vaccine is very important for your child."
Understanding that the side effects are minor and emphasizing the extensive research that vaccines must undergo can help parents feel reassured.
"HPV vaccine has been carefully studied by scientific experts. This is not a new vaccine and for years HPV vaccine has been shown to be very effective and very safe. Like other shots, side effects can happen, but most are mild, primarily pain or redness in the arm. This should go away quickly, and HPV vaccine has not been associated with any long-term side effects. Since 2006, about 57 million doses of HPV vaccine have been distributed in the U.S., and in the years of HPV vaccine safety studies and monitoring, no serious safety concerns have been identified."
Many parents do not know that the full vaccine series requires 3 shots. Your reminder will help them to complete the series.
"I want to make sure that your son/daughter receives all 3 shots of HPV vaccine to give them the best possible protection from cancer caused by HPV. Please make sure to make appointments on the way out, and put those appointments on your calendar before you leave the office today!"
Abstract: Squamous cell carcinomas (SCCs) of the vulva develop through human papilloma virus (HPV)-associated or HPV-independent pathways, but the relationship between pathogenesis, classification, and prognosis of these tumors is controversial. Therefore, we review the morphology, immunophenotype, and select molecular features of a consecutive series of 97 patients with vulvar SCC with a median clinical follow-up of 3.6 years. Tumors were histologically classified as basaloid (13), warty (11), mixed basaloid and warty (1), keratinizing (68), nonkeratinizing (3), and sarcomatoid (1). Diffuse p16 expression was associated with younger age at presentation (P<0.0001), basaloid and warty carcinoma subtypes (P<0.0001), and usual vulvar intraepithelial neoplasia (P<0.0001) and was negatively associated with p53 immunopositivity (P=0.0008). Five keratinizing SCCs showed p16 and p53 coexpression, but only 1 was positive for high-risk HPV by in situ hybridization. Among 8 of 36 tumors with EGFR gene amplification, 4 were p53 positive but none p16 positive. In a Cox regression model, early clinical stage (P<0.006), p16 expression (P=0.002), and absent p53 expression (P=0.02) were independent predictors of improved overall survival. These findings utilize morphologic and immunohistochemical analysis to support HPV-associated and HPV-independent pathogenesis of vulvar SCCs and support p16 and p53 immunohistochemistry as markers of disease biology and clinical outcome.
Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM
Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM
Heather Griffin, Yasmina Soneji, Romy Van Baars, Rupali Arora, David Jenkins, Miekel van de Sandt, Zhonglin Wu, Wim Quint, Robert Jach, Krzysztof Okon, Hubert Huras, Albert Singer and John Doorbar
Abstract: High-risk human papillomavirus (HPV) types cause cervical lesions of varying severity, ranging from transient productive infections to high-grade neoplasia. Disease stratification requires the examination of lesional pathology, and possibly also the detection of biomarkers. P16INK4a and MCM are established surrogates of high-risk HPV E6/E7 activity, and can be extensively expressed in high-grade lesions. Here we have combined these two cellular biomarkers with detection of the abundant HPV-encoded E4 protein in order to identify both productive and transforming lesions. This approach has allowed us to distinguish true papillomavirus infections from similar pathologies, and has allowed us to divide the heterogeneous CIN2 category into those that are CIN1-like and express E4, and those that more closely resemble nonproductive CIN3. To achieve this, 530 lesional areas were evaluated according to standard pathology criteria and by using a multiple staining approach that allows us to superimpose biomarker patterns either singly or in combination onto an annotated hematoxylin and eosin (H&E) image. Conventional grading of neoplasia was established by review panel, and compared directly with the composite molecular pathology visualized on the same tissue section. The detection of E4 coincided with the onset of vacuolation, becoming abundant in koilocytes as the MCM marker declined and cells lost their defined nuclear margins as visualized by standard H&E staining. Of the dual marker approaches, p16INK4a and E4 appeared most promising, with E4 generally identifying areas of low-grade disease even when p16INK4a was present. Extensive p16INK4a expression usually coincided with an absence of E4 expression or its focal retention in sporadic cells within the lesion. Our results suggest that a straightforward molecular evaluation of HPV life-cycle deregulation in cervical neoplasia may help improve disease stratification, and that this can be achieved using complementary molecular biomarker pairs such as MCM/E4 or, more promisingly, p16INK4a/E4 as an adjunct to conventional pathology.
Abstract: The history of “The Bethesda System” for reporting cervical cytology goes back almost 3 decades. This terminology and the process that created it have had a profound impact on the practice of cervical cytology for laboratorians and clinicians alike. Herein, we summarize the process and rationale by which updates were made to the terminology in 2014 and outline the contents of the new, third edition of the Bethesda atlas and corresponding website.
Abstract: Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16INK4a expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16INK4a staining like high-risk HPV–related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16INK4a expression.
The Pap Test and Bethesda 2014 “The reports of my demise have been greatly exaggerated.” (after a quotation from Mark Twain)
Nayar R., Wilbur D.C.
Abstract: The history of ‘The Bethesda System' for reporting cervical cytology goes back almost 3 decades. This terminology and the process that created it have had a profound impact on the practice of cervical cytology for laboratorians and clinicians alike. The Bethesda conferences and their ensuing output have also set the stage for standardization of terminology across multiple organ systems, including both cytology and histology, have initiated significant research in the biology and cost-effective management for human papillomavirus-associated anogenital lesions, and, finally, have fostered worldwide unification of clinical management for these lesions. Herein, we summarize the process and rationale by which updates were made to the terminology in 2014 and outline the contents of the new, third edition of the Bethesda atlas and corresponding website.
Women vaccinated with one dose of a human papillomavirus (HPV) vaccine had antibodies against the viruses that remained stable in their blood for 4 years, suggesting that a single dose of vaccine may be sufficient to generate long-term immune responses and protection against new HPV infections, and ultimately cervical cancer, according to a new study.
"The latest Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention on vaccination coverage indicates that in 2012, only 53.8% of girls between 13 and 17 years old initiated HPV vaccination, and only 33.4% of them received all three doses," said lead author Mahboobeh Safaeian, PhD, an investigator in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI) in Bethesda, Maryland.
"We wanted to evaluate whether two doses, or even one dose, of the HPV 16/18 L1 VLP vaccine [Cervarix] could induce a robust and sustainable response by the immune system," she added. "We found that both HPV 16 and HPV 18 antibody levels in women who received one dose remained stable 4 years after vaccination. Our findings challenge previous dogma that protein subunit vaccines require multiple doses to generate long-lived responses."
Data for this study are from the NCI-funded phase III clinical trial to test the efficacy of Cervarix in women from Costa Rica. The study was published in Cancer Prevention Research (2013; doi:10.1158/1940-6207.CAPR-13-0203).
About 20% of the women in the study received fewer than three doses of the vaccine, not by design. The researchers looked for the presence of an immune response to the vaccine (measured by antibody levels) in blood samples drawn from 78, 192, and 120 women who received one, two, and three doses of the vaccine, respectively, and compared the results with data from 113 women who did not receive vaccination but had antibodies against the viruses in their blood because they were infected with HPV in the past.
The researchers found that 100% of the women in all three groups had antibodies against HPV 16 and 18 in their blood for up to 4 years. Antibody levels were comparable for women receiving two doses 6 months apart and those receiving the full three doses.
The researchers also found that while antibody levels among women who received one dose were lower than among those who received the full three doses, the levels appeared stable, suggesting that these are lasting responses. In addition, the levels of antibodies in women from the one- and two-dose groups were 5 to 24 times higher than the levels of antibodies in women who did not receive vaccination, but had prior HPV infection.
“It is important to note that persistence of antibody responses after a single dose has not been evaluated for Gardasil, the quadrivalent HPV vaccine that is more widely used in the United States and many other countries," stated Safaeian.
Durable Antibody Responses Following One Dose of the Bivalent Human Papillomavirus L1 Virus-Like Particle Vaccine in the Costa Rica Vaccine Trial
Mahboobeh Safaeian1, Carolina Porras, Yuanji Pan, Aimee Kreimer, John T. Schiller, Paula Gonzalez, Douglas R. Lowy, Sholom Wacholder, Mark Schiffman1, Ana C. Rodriguez, Rolando Herrero, Troy Kemp, Gloriana Shelton, Wim Quint, Leen-Jan van Doorn, Allan Hildesheim, Ligia A. Pinto, for the CVT Group
Abstract: The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection.
Understanding Cervical Changes: A Health Guide for Women
Most women who have abnormal cervical screening tests do not have cervical cancer. Most have early cell changes that can be monitored, since they often go away on their own – or treated early, to prevent problems later. It is important to get the follow-up visits, tests, or treatment that your health care provider advises.
You can also access the information on this page as an e-book or PDF. Use this information to help you talk with your doctor after an abnormal cervical cancer screening result. If you have additional questions about cervical cancer screening, you may contact the National Cancer Institute.
Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability
Keiko Akagi, Jingfeng Li, Tatevik R Broutian, Hesed Padilla-Nash, Weihong Xiao, Bo Jiang, James W Rocco, Theodoros N Teknos, Bhavna Kumar, Danny Wangsa, Dandan He, Thomas Ried, David E Symer, and Maura L Gillison
Abstract: Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions and chromosomal translocations. We present a model of 'looping' by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.
Para muchas mujeres, la visita anual a su ginecólogo o médico de atención primaria incluye una prueba de Papanicolaou para detectar el cáncer de cuello uterino o lesiones que son precursores de la enfermedad. Nuevas evidenicas, sin embargo, demuestran que para muchas mujeres, la detección cervical anual, especialmente si también incluye un examen que detecte algunos de los tipos de virus del papiloma humano (VPH) es innecesario.
Varios grupos de oncología ginecológica de la salud vienen recomendado intervalos de 3 años para la detección del cáncer de cuello uterino en mujeres de 30 años o más que tienen una prueba de Papanicolaou normal y negativo de la prueba del VPH. Las recomendaciones, sin embargo, han no se ha aplicado en la práctica clínica habitual.
La prueba del VPH se utiliza para la detección en el cáncer cervical de la presencia de los tipos de VPH de alto riesgo. Los resultados de un amplio estudio de la práctica clínica habitual en el Kaiser Permanente Northern California, presentó 18 de mayo durante una rueda de prensa para el próximo Sociedad Americana de Oncología Clínica (ASCO) Reunión Anual Salida del sitio , ofrecen quizás la confirmación más fuerte hasta ahora de que una prueba anual de Papanicolaou ya no es una necesidad. En las mujeres de 30 años de edad o más que tenían una prueba de Papanicolaou normal y una negativa la prueba de ADN del VPH resultado, se detectaron muy pocos tipos de cáncer o cambios precancerosos en el siguiente período de 3 años, según el estudio.
"En la medida en que existe el temor sobre el riesgo de cáncer en un intervalo de exploración de 3 años, nuestro estudio reafirma los médicos y sus pacientes que este intervalo es seguro", dijo el investigador principal del estudio, el Dr. Hormuzd Katki del Instituto Nacional del Cáncer de la División de Epidemiología del Cáncer y Genética (DCEG).
El estudio encontró que la prueba de Papanicolaou no modificó sustancialmente el riesgo extremadamente bajo de cáncer para las mujeres VPH-negativas. Pero para las mujeres VPH positivas, la prueba de Papanicolaou ayudó a identificar mejor a las mujeres con alto riesgo de cáncer. Por lo tanto, dijo el Dr. Katki, los resultados también "presentan un fuerte hipótesis "de que la prueba del VPH podría llevarse a cabo en primer lugar, y, si es negativo, la mujer se le puede pedir para volver en 3 años. Si la prueba del VPH es positivo, la prueba de Papanicolaou puede ayudar a determinar si una mujer debe someterse a una colposcopia para examinar el cuello uterino para detectar signos de cáncer.
"Pero vamos a necesitar más estudio y la evaluación de esta posibilidad en la práctica clínica de rutina antes de que podamos estar seguros", dijo.
Un estudio del mundo real
El estudio es particularmente importante porque se trata de una "experiencia en el mundo real", dijo el presidente de ASCO Dr. George trineo durante la rueda de prensa. Se involucró a más de 330.000 mujeres en la región del Norte de California de Kaiser Permanente, una organización de atención administrada grande, por lo que es el mayor análisis de su tipo hasta la fecha.
"Este estudio nos dice hacia dónde vamos con la detección del cáncer", continuó, con la práctica de la transición de "una técnica milenaria como citopatología a las técnicas basadas más moleculares que nos permiten mirar realmente la causa específica de cáncer en pacientes con carcinoma de cuello uterino ".
Las mujeres del estudio habían inscrito voluntariamente en un programa co-test de VPH / Papanicolaou lanzado por Kaiser en 2003. Todas las mujeres en el programa se proyectó al año. Las mujeres con un resultado de la prueba de Papanicolaou normal y un resultado de la prueba del VPH negativa tuvieron una tasa de cáncer extremadamente bajo de 5 años, 3,2 cánceres por cada 100.000 mujeres por año. El cribado con sólo la prueba de VPH era casi tan eficaz, con 3,8 cánceres por cada 100.000 mujeres por año. Las estimaciones de riesgo para las mujeres con una prueba de Papanicolaou normal, solo eran casi el doble: 7,5 cánceres por cada 100.000 mujeres por año.
En comparación con la prueba de Papanicolaou positivo hacer solo, una prueba de VPH positiva solo hecho solo se asoció con una mayor probabilidad de encontrar cáncer o una lesión precancerosa después de 5 años, lo que significa que la prueba del VPH permitió la detección temprana de cáncer cervical o lesiones precancerosas.
Sin embargo, el Dr. Katki subrayó, la prueba de Papanicolaou positivo aportó información importante en las mujeres que también tenía una prueba de VPH positiva, aumentando la probabilidad de encontrar a las mujeres con cáncer establecido o los tipos de lesiones más probabilidades de convertirse en cáncer de cuello uterino.
¿Suficiente como para inclinar la balanza?
Incluso con las guías clínicas recomiendan co-pruebas e intervalos de cribado más largos y la acumulación continua de datos en apoyo de estas recomendaciones, cambiantes comportamientos médico ha sido muy difícil, dijo el Dr. Howard Jones, director de oncología ginecológica del Centro Oncológico Vanderbilt-Ingram en Nashville , TN. Aunque hay alguna evidencia que sugiere que los médicos han aumentado modestamente el uso de la prueba del VPH en conjunto con la prueba de Papanicolau, los estudios también indican que muchos han sido renuentes a extender los intervalos de cribado más allá de 1 año.
Tanto la lenta aceptación de la prueba del VPH y la incapacidad de ampliar los intervalos de cribado se puede atribuir a varios factores, el Dr. Jones continuó. Una de las razones más importantes para estos últimos es que muchas mujeres han llegado a esperar una prueba anual de Papanicolaou.
Los médicos pueden decirle a sus pacientes que tienen resultados negativos en ambas pruebas de que no es necesario que vuelva para el cáncer cervical durante 3 años. -Dr. Howard Jones
Los médicos pueden decirle a sus pacientes que tienen resultados negativos en ambas pruebas de que no es necesario que vuelva para el cáncer cervical durante 3 años, dijo, pero "cuando los pacientes regresan al año siguiente, y yo les digo que don ' t tiene que hacer una prueba de Papanicolaou, a menudo decir "No, yo quiero la prueba. '" Y añadió: "Como médico, no puedo discutir con una mujer durante 10 minutos, pero tengo 10 más pacientes para ver que mañana. Muchos médicos se acaba de hacer la prueba y ahorrar el tiempo y la frustración ".
Médico renuencia a ampliar los intervalos de cribado también se ha relacionado con los temores de que las mujeres no van a venir para chequeos anuales.
"El problema que muchos obstetras / ginecólogos tienen [con intervalos más largos] es que muchas mujeres piensan en gran medida la única razón para ir a un médico para una prueba de Papanicolaou", dijo el Dr. Ellen Smith, un oncólogo ginecológico con Texas Oncology, en Austin. "Para muchas mujeres, que es la única vez que obtienen su presión arterial, su peso marcada, acaba de obtener un examen físico general." Una proporción importante de las mujeres que ya no ven a un médico de cabecera o ginecólogo / obstetra regularmente, el Dr. Smith continuó . "Entonces, ¿qué va a ser como si [el cáncer cervical] intervalo de cribado es cada 3 años?"
Mientras tanto, el Dr. Smith destacó, también es necesario que haya un enfoque intenso en la otra cara de la moneda: asegurar que las niñas y las mujeres jóvenes reciban la vacuna contra el VPH para prevenir el cáncer de cuello uterino en el primer lugar y el aumento del número de mujeres que son evaluados periódicamente. Más de la mitad de las mujeres diagnosticadas con cáncer de cuello uterino no se han proyectado en los 5 años anteriores, dijo.
Debido a que las vacunas contra el VPH actuales evitarán sólo el 70 por ciento de los cánceres de cuello uterino, el Dr. Katki subrayó que las guías actuales recomiendan que las mujeres que se vacunan todavía deben ser examinadas mediante citologías periódicas.
En todas estas cuestiones, dijo el doctor Jones, "Realmente necesitamos educar a los médicos, educar a los pacientes, y seguir empujando hacia adelante."
- Carmen Phillips
VPH y cáncer de laringe
Correlation of Laryngeal Squamous Cell Carcinoma and Infections with Either HHV-8 or HPV16/18
Nema Mohamadian Roshaa, Amirhossein Jafariaa, Hossein Ayatollah, Kiarash Ghazvini, Seyyed Abbas Tabatabaee
Abstract: Each year more than 159,000 new cases of laryngeal cancer are diagnosed globally, and more than 9000 patients die due to this malignancy. Viral infections are a known risk factor for this malignancy. Thus, this study aimed to evaluate the role of HPV-16/18 and HHV-8 infection in patients with laryngeal cancer. In this case–control study, 60 formalin-fixed, paraffin-embedded samples of laryngeal cancer and 22 normal larynx tissue samples from the Pathology Department of Qaem Hospital, Mashhad, Iran were studied. After validating the diagnosis, the samples were evaluated for the detection of HPV-16/18 and HHV-8 DNA using PCR technique. The data were registered and analyzed using SPSS 18.0. The average age for patients and controls was 61.29 ± 11.89 and 55.77 ± 10.10, respectively. Fifty-four patients (90%) and 16 (72.7%) controls were male. PCR results detected no HPV-16/18 DNA in both groups. Although there were 2 positive HHV-8 samples in both laryngeal cancer and normal larynx samples, no significant relation was present (p = 0.291). We found no significant relationship between infection with HHV-8 or HPV-16/18 and the existence of laryngeal cancer. However, more complementary studies are required to re-evaluate our results using more samples and better viral detection techniques.
El artículo original de ésta nota de prensa es el siguiente:
RESEARCH Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data
Hammad Ali, Basil Donovan, Handan Wand, Tim R H Read, David G Regan, Andrew E Grulich, Christopher K Fairley, Rebecca J Guy
Abstract: Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Design Trend analysis of national surveillance data. Setting Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Participants Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Main outcome measure Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Results Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period—from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period—from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. Conclusions: The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.
Factors associated with human papillomavirus vaccination among young adult women in the United States.
Williams WW, Lu PJ, Saraiya M, Yankey D, Dorell C, Rodriguez JL, Kepka D, Markowitz LE.
Abstract. BACKGROUND: Human papillomavirus (HPV) vaccination is recommended to protect against HPV-related diseases.
OBJECTIVE: To estimate HPV vaccine coverage and assess factors associated with vaccine awareness, initiation and receipt of 3 doses among women age 18-30 years. METHODS: Data from the 2010 National Health Interview Survey were analyzed to assess associations of HPV vaccination among women age 18-26 (n=1866) and 27-30 years (n=1028) with previous HPV exposure, cervical cancer screening and selected demographic, health care and behavioral characteristics using bivariate analysis and multivariable logistic regression. RESULTS: Overall, 23.2% of women age 18-26 and 6.7% of women age 27-30 years reported receiving at least 1 dose of HPV vaccine. In multivariable analyses among women age 18-26 years, not being married, having a regular physician, seeing a physician or obstetrician/gynecologist in the past year, influenza vaccination in the past year, and receipt of other recommended vaccines were associated with HPV vaccination. One-third of unvaccinated women age 18-26 years (n=490) were interested in receiving HPV vaccine. Among women who were not interested in receiving HPV vaccine (n=920), the main reasons reported included: not needing the vaccine (41.3%); concerns about safety of the vaccine (12.5%); not knowing enough about the vaccine (11.9%); not being sexually active (8.2%); a doctor not recommending the vaccine (7.6%); and already having HPV (2.7%). Among women with health insurance, 10 or more physician contacts within the past year and no contraindications, 74.5% reported not receiving HPV vaccine. CONCLUSIONS:
HPV vaccination coverage among women age 18-26 years remains low. Opportunities to vaccinate are missed. Healthcare providers can play an important role in educating young women about HPV and encouraging vaccination. Successful public health and educational interventions will need to address physician attitudes and practice patterns and other factors that influence vaccination behaviors.
Three vaccines are approved by the FDA to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70 percent of cervical cancers and an even higher percentage of some of the other HPV-associated cancers (warts (quadrivalent vaccine. Gardasil 9 prevents infection with the same four HPV types plus five additional high-risk HPV types (31, 33, 45, 52, and 58) and is therefore called a nonavalent, or 9-valent, vaccine. All three vaccines are given through a series of three injections into muscle tissue over a 6-month period.
The FDA has approved Gardasil and Gardasil 9 for use in females ages 9 through 26 for the prevention of HPV-caused cervical, vulvar, vaginal, and anal cancers; precancerous cervical, vulvar, vaginal, and anal lesions; and genital warts. Gardasil and Gardasil 9 are also approved for use in males for the prevention of HPV-caused anal cancer, precancerous anal lesions, and genital warts. Gardasil is approved for use in males ages 9 through 26, and Gardasil 9 is approved for use in males ages 9 through 15.
The Cervarix vaccine is produced by GlaxoSmithKline (GSK). It targets two HPV types16 and 18and is called a bivalent vaccine. The FDA has approved Cervarix for use in females ages 9 through 25 for the prevention of cervical cancer caused by HPV.
In addition to providing protection against the HPV types included in these vaccines, the vaccines have been found to provide partial protection against a few additional HPV types that can cause cancer, a phenomenon called cross-protection. The vaccines do not prevent other sexually transmitted diseases, nor do they treat existing HPV infections or HPV-caused disease.
Because currently available HPV vaccines do not protect against all HPV infections that cause cancer, it is important for vaccinated women to continue to undergo cervical cancer screening. There could be some future changes in recommendations for vaccinated women.
XII International Workshop of Lower Genital Tract Pathology
Antonio Frega, Philip Davies and I, Cesare Gentili, are pleased to announce the XII Workshop of Lower Genital Tract Pathology which will be held in Rome from March 5th to 7th 2015. These Workshops have a unique multidisciplinary nature covering all disciplines related to diseases of the lower genital tract. The last Workshop was attended by over 500 participants from 39 countries and with 55 speakers of international renown who maintained the participants’ interest for the entire congress by delivering a challenging and comprehensive program. We have no doubt that the upcoming congress will be an even bigger success. For 2015, we have made some changes to the program by introducing some innovative elements in order to make it a more dynamic workshop while still keeping a sharp focus on the new issues that are of interest to clinicians and scientific validity. More time will be allowed for debates, particularly in the specialized sessions on topics of interest in daily practice. There will be four interactive sessions, two for gynaecologists and two for pathologists, that will be based on clinical cases presentations using slides and videos. In each specialisation, one session will be led by the speakers and the other by the participants who will present previously selected cases. And there will be the new Twitter style Sessions, an effective way to summarize the salient points of the day. After the success of the “Free Communications” in the previous Workshop, we have decided to repeat it this year too. Prizes will be given to the best three communications during the plenary session. Moreover, the participants will have the opportunity to vote for their favourite speaker and prizes will be given to the best three. The multidisciplinary nature of the Workshop will allow experts from different fields to follow the topics of common interest in the plenary session as having the opportunity to learn about the latest development in their own specialist areas. The program will have a logical progression without duplications or overlap. As in previous Workshop, the XII edition will have lectures covering the latest issues in cervical cancer prevention, diagnosis and treatment, and it will have the most highly respected researchers and clinicians from Italy and the rest of the world. Although the congress has an international character, the atmosphere is informal and simple, and you can spend some pleasant days in Rome with us enjoying the typical dishes of the evocative Roman restaurants.
We now look forward to welcoming you to the XII Workshop of Lower Genital Tract Pathology in Rome next year.