The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology

Abstract

The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

“…Concordant results included in the study were in the following three diagnostic categories: (a) negative: women with a negative Pap test result for intraepithelial lesion or carcinoma, a negative result in biopsy and negative high-risk HPV testing (n ¼ 28); (b) LSIL: women with a Pap test result of LSIL, a biopsy showing LSIL and a positive high-risk HPV testing (n ¼ 47); and (c) HSIL: patients with Pap test result of HSIL, biopsy confirming HSIL and positive high-risk HPV testing (n ¼ 48). 6 The exclusion criteria were as follows: (1) histological diagnosis of carcinoma or previous history of CC; (2) previous treatment for CIN2-3 performed within the previous 3 years; (4) pregnancy; (5) previous HPV vaccine, and (6) discordant results in cytology, histology, and Hybrid Capture 2 testing (eg patients with Pap test result of HSIL and biopsy with LSIL or negative result or women with positive high-risk HPV and normal cytology).…”

“…In most women with these low-risk lesions, both high-risk HPV infection and the epithelial abnormalities are cleared within a few months or years (transient infections). Therefore, there is a need to explore new more specific techniques that may help to identify the subset of women harboring high-grade squamous intraepithelial lesions (HSIL), 6 the true precursor of CC, from the broad group of women testing positive for a high-risk HPV.…”

P16INK4A immunostaining is a strong indicator for high‐risk‐HPV‐associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low‐risk‐HPV‐infection in head and neck papillomas and laryngeal dysplasias

“…23 Controls included sections of uterine cervical IN grade 2 and 3 (positive controls) and sections from the same cases on which the p16 INK4A antibody was substituted by a monoclonal mouse IgG2a antibody to Aspergillus Niger or by buffer without a primary antibody (negative controls).…”

“…As such, the method is used as an adjudication tool for cases in which there is a professional disagreement in histologic specimen interpretation. 23 Despite the fact that p16 INK4A immunohistochemistry is a low-cost test that can easily be implemented in daily diagnostic practice, its reliability as a surrogate marker for the presence of HR-HPV has been subject of debate. 18,24 HPV-negative but p16 INK4A positive cases, although small in number, have been described in many series.…”

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix

“…2 High-grade SIL/CIN grades 2-3 (HSIL/CIN2-3) are considered the immediate precursor of cervical cancer. 3 In contrast, about 80% of low-grade SIL/CIN1 (LSIL/CIN1) are transient lesions that generally spontaneously regress in 1-2 years.…”