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HPV 6-associated HSIL/Squamous Carcinoma in the Anogenital Tract

Liu, Martina Z. M.D.; Hung, Yin P. M.D., Ph.D.; Huang, Eric C. M.D., Ph.D.; Howitt, Brooke E. M.D.; Nucci, Marisa R. M.D.; Crum, Christopher P. M.D.

International Journal of Gynecological Pathology: September 2019 - Volume 38 - Issue 5 - p 493–497
doi: 10.1097/PGP.0000000000000556
Pathology of the Lower Genital Tract: Original Article

Human papillomavirus (HPV) type 6 is historically classified as low-risk HPV type and associates with low-grade squamous intraepithelial lesions of the anogenital tract. Rare squamous carcinomas have been reported in association with these HPV types but the mechanism(s) behind this carcinogenic sequence have been unclear. We report 4 cases of low risk anogenital HPV infections—3 cervical (immature low-grade squamous intraepithelial lesion with metaplastic phenotype) and one anal (exophytic condyloma) lesion—that manifested with high-grade squamous intraepithelial lesion/squamous cell carcinoma. Two were associated with invasion one of which metastasized to a regional node. Two cases exhibited strong p53 positivity in the high-grade squamous intraepithelial lesion/squamous cell carcinoma component analogous to that seen in HPV-negative differentiated intraepithelial lesions of the external genitalia. This series of cases adds to the literature on low risk HPV-associated cervical squamous carcinomas. It underscores the similarities between the baseline cyto-morphology and benign mimics (low-grade squamous intraepithelial lesions), the subtle cytologic and immunohistochemical (MIB1) features heralding biologic aggressiveness, and in some potential pathways (p53) not usually involved in HPV-related anogenital neoplasia.

Department of Pathology, Division of Women’s and Perinatal Pathology, Brigham and Women’s Hospital, Boston, Massachusetts (M.Z.L., Y.P.H., M.R.N., C.P.C.)

Department of Pathology, Division of Cytopathology, University of Washington Health Sciences Center, Seattle, Washington (E.C.H.)

Department of Pathology, Stanford University Medical Center, Palo Alto, California (B.E.H.)

M.Z.L., Y.P.H., M.R.N., and C.P.C, shared equally as first and senior authors, respectively.

The authors declare no conflict of interest.

Address correspondence and reprint requests to Christopher P. Crum, MD, 75 Francis Street, Boston, MA 02115. E-mail:

©2019International Society of Gynecological Pathologists