The Lower Anogenital Squamous Terminology Standardization Project for HPV-associated Lesions

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 co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three 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 upon 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 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.

Evaluating HPV‐negative CIN2+ in the ATHENA trial

“…In a second phase of the analysis, all cobas‐negative CIN2+ cases underwent p16 immunostaining 9. As overexpression of p16 in cervical lesions is a consequence of a transforming HPV infection, p16‐positive cobas‐negative cases could be best explained by false‐negative HPV or false‐positive histology results.…”

Squamous Intraepithelial Lesions in Cervical Tissue Samples of Limited Adequacy and Insufficient for Grading as Low or High Grade

“…Two pathologists who were masked to the original and review diagnoses together scored the IHC staining until agreement was reached. Published scoring systems for both biomarkers depend on the presence of a basal layer of squamous epithelium or a basement membrane [10,11]. System 1 was faithful to the published criteria, but System 2 was a modification to accommodate SIL without a basal layer or basement membrane.…”

“…Expression status among satisfactory scores was then categorized as negative (score 0, 1, and 2) and positive (score 3). In System 2, p16 INK4a expression was categorized as positive when the entire SIL lesion stained or when ''block positive staining,'' defined as continuous strong staining of the basal cell layer extending upward to involve at least one third of the epithelial thickness, was present [11]. Expression status was negative when neither pattern was present.…”

“…The Lower Anogenital Tract Squamous Terminology Standardization Project for HPV-Associated Lesions (LAST) did not recommend a term for this lesion, although it emphasized that SIL in small fragments, tangential cuts, and free-floating single cells may be subject to observer variability [11]. The Pan-Canadian Cervical Screening Initiative of the Canadian Partnership Against Cancer in 2013 endorsed the LAST terminology but recommended using the term ''ungraded SIL'' (SILQ) for the reporting of SIL in tissue samples of limited adequacy [12].…”

The Pap Test and Bethesda 2014

“…The 2-tiered terminology of LSIL and HSIL used in TBS is now also recommended by the World Health Organization, the ASCCP, and the College of American Pathologists for reporting histopathology of HPV-associated squamous lesions of the lower anogenital tract [16,17,18,19]. …”