Human papillomaviruses (HPVs) play a major role in the development of genital neoplasia. Their role in anal carcinogenesis is less clear, and the rate of HPV genome detected in invasive anal carcinoma varies considerably in the different reports. Moreover, the relationship of HPV to basaloid carcinoma, claimed to represent a histologic type different from the common squamous cell carcinoma, is still controversial. By use of both polymerase chain reaction and Southern blot hybridization on DNA extracted from frozen tissue specimens, we looked for HPV sequences in 12 cases of squamous cell carcinoma, in 9 cases of basaloid invasive carcinoma, in 1 case of carcinoma in situ, and in 1 case of Paget's disease of the anal canal. We have looked for correlations between virologic data and histologic types of tumors, and analyzed the clinical characteristics of HPV-positive and HPV-negative lesions. In our series, 20 (74%) of 27 cases of invasive anal carcinoma were positive for HPV DNA by Southern blot hybridization and/or polymerase chain reaction. HPV 16 DNA was found in 17 cases, HPV 18 in 2 cases, and in 1 case, the type of the HPV sequences detected remained undetermined (HPV X). Histovirologic correlations showed that 12 of 18 squamous cell carcinomas were associated with HPV 16 and that 8 of 9 cases of basaloid carcinoma were HPV positive; 5 case corresponded to HPV 16, 2 cases to HPV 18, and 1 case to HPV X. The carcinoma in situ case and the Paget's disease case were negative. An analysis of these data within the framework of the literature indicates that approximately 75% of cases of invasive anal carcinoma can actually be considered associated with HPV sequences. Basaloid carcinoma is also frequently associated with HPV genomes and is more likely to represent a histologic variant of squamous cell carcinoma than a separate entity. No clinical characteristics related to the HPV status of the tumors were observed in our series. Epidemiologic data on cervical, anal, and vulvar neoplasia are compared and their relation to the oncogenic properties of HPV in these different tissues are discussed.