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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]
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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

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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



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Big data is about to get bigger. And more meaningful for you. CancerLinQ is assembling vast amounts of usable, searchable, real-world cancer information into a powerful database. This national initiative was inspired and informed by the cancer experts at ASCO, so it's not merely an exercise in IT; this is intuitively tuned to deliver what you need. Imagine searching and seeing trends among millions of patients with almost every treatment, tumor type, and genomic profile. This is big data that can improve quality of care for patients—every single one. And that's a number to be proud of.

CancerLinQ can contribute to high-quality, personalized cancer care for every patient.


Aumento de incidencia de Cáncer de Colon y su conexión con el VPH

Dr. Monica Malik

Rising Rates of Sporadic Colorectal Cancer in Young Adults: A Possible Environmental by Dr. Monica Malik

Key Points

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.

Fuente: ASCO Daily News, May 30, 2015