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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; number, NCT00543543).

Source: New England Journal of Medicine, February 18, 2015

Fuente: Tweet de @theNCI - Pubmed

Squamous Cell Carcinoma of the Vulva: A Subclassification of 97 Cases by Clinicopathologic ...

Squamous Cell Carcinoma of the Vulva: A Subclassification of 97 Cases by Clinicopathologic, Immunohistochemical, and Molecular Features (p16, p53, and EGFR)

Dong, Fei; Kojiro, Sakiko; Borger, Darrell R.; Growdon, Whitfield B.; Oliva, Esther

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.

American Journal of Surgical Pathology: August 2015 - Volume 39 - Issue 8 - p 1045–1053

Fuente: Tweet de @memoalexlope

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.

These patients have different demographic patterns, in that they are more likely to be younger, white adults in their 40 s and 50 s who are never smokers or have reduced tobacco exposure. Studies have shown that a higher number of lifetime oral sex partners (>5) and a higher number of lifetime vaginal sex partners (>25) have been associated with increased risk of HPV positive head and neck cancer. People can also reduce their risk of HPV linked head and neck cancer by receiving the HPV vaccine series prior to becoming sexually active. Recent evidence suggests HPV related head and neck cancers present with different symptoms than those caused by tobacco. The most popular test for HPV status is the p16 immunohistochemical stain because it is cheap, simple, and studies have shown it to have comparable sensitivity and specificity to the previous standards. It is widely recommended that all cancers of the oropharynx be tested for the presence of HPV, and some recommend it for all head and neck cancers. Overall 2-year and 5-year survival for HPV positive head and neck cancer is significantly greater than for HPV negative cancers, likely due to HPV positive cancers being more responsive to treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

PMID: 26066977
Oral Oncol 2015 Aug;51(8):727-30 [EPub Ahead of Print]
Tweet de @memoalexlope

TRIG Working Group

Preparing Pathologists for a Leading Role in Genomics


In 2010, the Training Residents in Genomics (TRIG) Working Group was formed through the Pathology Residency Directors Section (PRODS) of the Association of Pathology Chairs (APC). The goals of this group, made up of experts in medical education, molecular pathology, and clinical genetics, are to develop teaching tools, and promote genomic pathology education. The TRIG Working Group represents a unique collaborative effort in pathology education with members from many major pathology organizations and representatives from the National Society of Genetic Counselors, American College of Medical Genetics and Genomics, and the National Coalition for Health Provider Education in Genetics.

The TRIG Working Group has held genomic pathology workshops and courses at the annual meetings of major pathology organizations. An Instructor Handbook and Toolkit are now available to enable residency programs to locally implement similar training.

Based on their accomplishments, the TRIG Working Group received in 2012 an R25 grant from the National Cancer Institute. Providing approximately $1.3 million over five years, this funding will be used, with design support from ASCP, to develop additional educational resources such as online modules as well as assessment tools to determine curriculum efficacy. The specific aims of the grant are:

  • Aim #1.- To develop a pathology resident genomic medicine curriculum, with a major focus on cancer care, as well as tools for national implementation.”
  • Aim #2.- To evaluate the curriculum using a pre/post-test design at four pathology residency programs using validated assessment tools.”
  • Aim #3.- To promote curriculum implementation using the resources of major national pathology organizations so that >90% of pathology residency programs nationwide have high-quality training in cancer genomics by the end of year 5.”
  • Aim #4.- To assess the degree of nationwide implementation and efficacy of curricula in genomic medicine using the pathology resident in-service exam (RISE).”


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.

Modern Pathology 28, 977-993 (July 2015) | doi:10.1038/modpathol.2015.52

¿Qué hace un patólogo?


The College of American Pathologists (CAP), the leading organization of board-certified pathologists.

Northfield, IL

Fuente: Tweet de @Pathologists


RENAL DISEASE AND CARDIOVASCULAR RISK: A GLOBAL VIEW - Nephrology Division. Hospital Italiano de Buenos Aires. Argentina [Rev Electron Biomed]


TROMBOCITOPENIA ALOINMUNE DEL FETO Y EL NEONATO: A PROPÓSITO DE 2 CASOS - Servicio de Pediatría, del Centro de Salud Gamonal-Antigua. Servicio de Hematología-Hemoterapia. Hospital Universitario de Burgos. Burgos. España [Rev Electron Biomed]

La OMS informa sobre la gripe asiática (en inglés)

Frequently Asked Questions on Middle East respiratory syndrome coronavirus (MERS‐CoV)

12 June 2015


Fuente: Tweet de @WHO - OMS/WHO


CONSIDERACIONES SOBRE MODELOS DE FORMACIÓN Y PRÁCTICA MÉDICAS. ¿INNOVACIÓN O RENOVACIÓN? - EDITORIAL /EDITORIAL. Profesor Honorario de la Facultad de Ciencias Médicas y Miembro del Consejo de Investigaciones de la
Universidad Nacional de Rosario. Rosario. Argentina.
[Rev Electron Biomed]

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.

Fuente: Tweet de @CDCSTD - CDC FACT SHEET

The 2014 Bethesda System

Cancer Cytopathology
The Pap test and Bethesda 2014

Ritu Nayar MD and David C. Wilbur

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.

Cancer Cytopathology 2015; 123(5):271–281

Sobre la vacuna del VPH

Tips and Time-savers for Talking with Parents About HPV Vaccine
CDC research shows these straightforward messages are important to parents when discussing HPV vaccine-and easy for you or your staff to deliver. 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.

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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."

Carcinogenic HPV infection in the cervical squamo-columnar junction

Carcinogenic HPV infection in the cervical squamo-columnar junction

Mirkovic J, Howitt BE, Roncarati P, Demoulin S, Suarez-Carmona M, Hubert P, McKeon FD, Xian W, Li A, Delvenne P, Crum1 CP, Herfs M

Abstract: Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16ink4, Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16ink4 and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16ink4 immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16ink4 expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Journal of Pathology. 2015; 236(3):265–271 DOI: 10.1002/path.4533