Causative Human Papillomavirus (HPV) Genotypes of Anal Cancers in Australian Cisgender Women

Anal cancer, caused by persistent infection with oncogenic human papillomavirus (HPV), is rare in the general population. However, certain groups, such as men who have sex with men living with HIV, are at much higher risk, and research into the etiology and pathogenesis of the disease has focused on this group. Other high-risk groups, such as women with a history of gynecological HPV-related disease, have been neglected. While single anal cancer lesions typically contain one HPV genotype, multiple genotypes are often detected in anal swabs, complicating attribution. Identifying the causal genotype is essential to assessing the potential impacts of HPV vaccination programs. This study used laser capture microdissection (LCM) to identify the lesion-specific HPV genotype in anal squamous cell carcinomas from women. Thirty-five anal cancer samples from women were drawn from the Anal Cancer Outcomes Research Network - Baseline Study (ACORN). Five were excluded, leaving 30 specimens from cisgender women for analysis. p16 immunostaining confirmed high-risk HPV infection; HPV genotyping using the HPV SPF10-LiPA25 kit identified the causal genotype for each cancer. The median age at diagnosis was 58.5 (IQR 48-72). All specimens contained a single HPV genotype: 93.3% HPV16, 3.3% HPV18, and 3.3% HPV31. To our knowledge, this is the first study to use LCM on anal cancer biopsies from women to attribute a causal HPV genotype. All specimens tested positive for a single genotype, with HPV16 causing almost all cancers. All cases in this sample could potentially have been prevented by nonavalent prophylactic vaccination, and 97% by the quadrivalent vaccine.