Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses

High-risk types of human papillomaviruses (hrHPVs) may be a necessary cause in cervical cancer and in some subtype of anal, vulvar, and penile cancers . Large studies aimed at characterizing hrHPV-associated and non-hrHPV-asso ciated subtypes of anal carcinomas are, however, lacking. We searched for h uman papillomavirus type 16 and 13 other hrHPVs in tumor tissue by PCR and performed a systematic histological evaluation of specimens from 386 patien ts with anal cancer (86% invasive; 302 women and 84 men). Cancers in women and homosexual men were more often hrHPV positive (P < 0.01) and located in the anal canal (P less than or equal to 0.01) than were cancers in heteros exual men. In both women and men, anal canal cancers contained hrHPV clearl y more often than did perianal skin cancers, and increasing hrHPV positivit y was seen with higher localization in the anal canal. Indeed, 95 and 83% o f cancers involving the anal canal in women and men, respectively, were hrH PV positive versus 80 and 28% of perianal skin cancers (P-trend < 0.001). B asaloid feature, adjacent anal intraepithelial neoplasia, poor or absent ke ratinization, and a predominance of small or medium neoplastic cells were a ll strongly positively associated with hrHPV status. Like cancer of the ute rine cervix, the development of cancer of the anal canal may require infect ion with hrHPV, whereas a dual etiology of perianal skin cancers bears para llels to vulvar and penile cancers.