College of American Pathologists
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  President’s Desk


CAP Today

Stanley J. Robboy MD, FCAP
Stanley J. Robboy, MD




July 2012

Stanley J. Robboy, MD

LAST project launches new era

On June 28, the Lower Anogenital Squamous Terminology (LAST) Standardization Project for HPV-associated lesions, cosponsored by the CAP and American Society for Colposcopy and Cervical Pathology, issued consensus recommendations that will provide a standardized histopathologic terminology for human papillomavirus-associated squamous lesions of the lower anogenital tract (published online ahead of print in Archives of Pathology & Laboratory—and Journal of Lower Genital Tract Disease). The recommendations provide reliable advice on the appropriate use of biomarkers to more reliably diagnose these lesions, including specific guidance on more judicious use of biomarker p16. Overall, the goals of the LAST project are to provide improved diagnostic communication between pathologists and treating clinicians.

The most important risk factor for cervical cancer is HPV infection, which can affect not only the cervix but also the vagina, vulva, anal canal, perianus, and penis. And HPV is the most common sexually transmitted infection in the United States; the Centers for Disease Control and Prevention estimates that 20 million Americans are currently infected.

The project was undertaken in recognition that terminology does influence management of these lesions in important ways. The project’s recommendations will lead to more consistent pathologic reporting and enable physicians to better evaluate the risks and benefits of patients’ options, including conservative followup or colposcopy, and more accurately assess the risk of developing more serious disease.

The nomenclature for squamous dysplasias and early cancers of the lower anogenital tract is controversial. Currently, various subspecialties in different fields use multiple terminologies. Over the last two decades, our understanding of the biology and molecular makeup of HPV-related squamous disease, including neoplasms, has improved dramatically. This, in turn, made it clear that a harmonized diagnostic terminology was needed to enable effective communication between pathologists and other clinicians, enable more effective patient management, avoid overtreatment, and improve patient outcomes.

The intersection of these developments created an opportunity for the CAP Pathology and Laboratory Quality Center, which provides a forum to create and maintain evidence-based practice guidelines and consensus statements. Fortuitously, the CAP Transformation Program Office Steering Committee, which launches and guides Center projects, had recently put out a call for proposals.

David C. Wilbur, MD, director of the clinical imaging service at Massachusetts General Hospital and a professor of pathology at Harvard Medical School, queried the CAP Cytopathology Committee, which he chaired at the time. Teresa Darragh, MD, proposed what would become the LAST project.

Dr. Darragh is a professor of clinical pathology and obstetrics, gynecology, and reproductive sciences at the University of California San Francisco and an attending physician in the UCSF/Mt. Zion Dysplasia Clinic. She is also president-elect of the ASCCP. Experience in the colposcopy clinic had given Dr. Darragh the necessary passion to drive her idea home. When the Transformation Program Office Steering Committee gave the green light, Drs. Wilbur and Darragh were asked to co-chair the LAST Project Steering Committee.

The mission was fourfold:

  • To approve standardized terminology for reporting histopathology diagnoses of HPV-related mucocutaneous squamous lesions of the lower anogenital tract, including intraepithelial lesions and minimally invasive cancers;

  • To harmonize terminology across the various lower anogenital tract sites with current evidence-based knowledge regarding the biology of HPV-related squamous lesions and their clinical management;

  • To harmonize the terminology for histopathology with the Bethesda System for reporting gynecologic and anal cytology (if applicable); and

  • To assess the use of biomarkers to validate proposed terminology standards and provide recommendations for appropriate use of biomarkers, in particular p16.

Forty-three representatives and 14 advisors formed a multidisciplinary panel of experts and thought leaders in the field, drawing from pathology and direct patient care specialties, including dermatology, gynecology, surgery, urology, infectious disease, and medical oncology. The five work groups addressed historical aspects, intraepithelial lesions, minimally invasive cancers, molecular markers, and implementation and dissemination.

Altogether, the work groups scanned 6,063 abstracts, read 1,210 full text articles, completed 452 data extractions, and ultimately provided 18 recommendations and definitions for a proposed standardized terminology. The CDC, Food and Drug Administration, and National Cancer Institute were among 35 national and international professional organizations that participated in the deliberations, revisions, and final approval of consensus recommendations in San Francisco in March 2012.

One gratifying moment occurred when the assembly of voting members considered whether p16 immunohistochemistry as a routine adjunct helps or hinders the diagnosis of low-grade and high-grade morphologies. In voting unanimously to confirm that p16 IHC helps where there is an intermediate morphologic interpretation, including dysplasia look-alikes such as atrophy, they confirmed the importance of pathologists as consummate morphologists.

Implications and implementation are the purview of Work Group 5, co-chaired by Ronald D. Luff, MD, director of anatomic pathology for clinical trials at Quest Diagnostics, and Ritu Nayar, MD, a professor of pathology and director of cytopathology at Northwestern University Feinberg School of Medicine. Their many plans include an online atlas that will provide useful images and accommodate self-assessment. Several major journals will carry reports and editorials about the LAST project, and Drs. Wilbur and Darragh will present at CAP ’12. Practice surveys are planned to assess current practice and track how the recommendations are implemented.

CAP members will have an important role in adoption of the LAST recommendations and nomenclature. Please implement the consensus recommendations in your institutions and educate your clinical colleagues. This final step will validate all the work that has come before it.

Center projects underscore the importance of pathologists in clinical care and emphasize the essential part we play in effective and value-driven medicine. At the consensus conference, the level of passion and collegiality around getting this right for our patients was exhilarating. Congratulations are due to all—pathologists and other clinicians—whose hard work produced this seminal document and to the CAP and ASCCP staff who made it possible.

Dr. Robboy welcomes communication from CAP members. Send your letters to him at