Anal and perianal squamous carcinomas and high-grade intraepithelial lesions exclusively associated with "low-risk" HPV genotypes 6 and 11

Anal squamous cell carcinomas are predominantly associated with high-risk human papillomaviruses (HPVs), particularly HPV 16, similar to cervical, vaginal and vulvar cancers. Although the presence of low-risk HPVs, in particular genotypes 6 and 11, have occasionally been reported in various HPV-related anogenital cancers, the overall distribution of these genotypes in the anal canal and perianal tissue may differ to that in the cervix. In addition, although the majority of anal and perianal cancers are associated with HPV, some are not; hence, confirmation of direct association of the virus within a lesion is important. Using laser capture microdissection, anal and perianal invasive carcinomas and high-grade squamous intraepithelial lesions (HSILs) in biopsies previously associated with HPV 6 or 11 alone were isolated from tissue sections and HPV genotype tested. Of seven cases tested, four invasive carcinomas were positive for HPV 6 only, one invasive carcinoma was negative for HPV and two HSILs were positive for HPV 11 only. All samples were confirmed as HPV 16/18 negative using two different DNA targets (E6 and L1). From these results, we confirm that HPV 6 and 11 can occasionally be associated with high-grade lesion and anal cancer. What's new? Reports of invasive cancers caused exclusively by strains of low-risk human papillomavirus (HPV) are extremely rare. This report describes six cases of anal and perianal invasive squamous cell carcinomas and high-grade squamous intraepithelial lesions associated exclusively with low-risk HPV genotypes. The cases were detected using laser capture microdissection of biopsy specimens. The findings suggest that HPV 6 and 11 may be responsible for occasional instances of high-grade lesions and may have oncogenic capacity, resulting in anal and perianal squamous cell carcinoma.