PURPOSE:The wild‐type P53 protein, a product of theP53gene, is a normal growth controlling protein. Mutation of theP53gene generates a mutant P53 protein which promotes tumor formation through loss of growth suppression. Some of the agents responsible forP53gene mutation are known, one of which may be tumorigenic human papillomavirus (HPV) infection. Anal cancers are demonstrating a changing trend in the affected population, from older females in the older reported series to younger males more recently. This may be a reflection of infection with tumorigenic HPV types 16 and 18. The E6 oncoprotein of these viruses inactivates the growth‐controlling wild‐type P53 protein. In this study, our purpose was to determine the incidence of mutant P53 and HPV‐16 and 18‐related E6 protein and their coexpression in anal cancers.METHODS:We examined 29 anal cancers immunohistochemically for mutant P53 protein, HPV 16 and 18 E6 protein, and coexpression of the two.RESULTS:Mutant P53 protein was present in 58.6 percent of anal cancers overall and in 85.7 percent of anal adenocarcinomas. E6 oncoprotein was present in five cases (17.2 percent), all of which were squamous‐cell carcinomas. Coexpression of both mutant P53 and E6 proteins was seen in only three cases (10.3 percent).CONCLUSION:Although tumorigenic HPV may be an important cause forP53gene mutation in anal cancers, perhaps other mutagenic factors play a predominant role.