PURPOSE:With improved antiretroviral therapy, HIV‐positive patients are achieving a longer life expectancy. An increased incidence of anal squamous cell carcinomas has been noted in these patients. The purpose of this study was to determine the outcome of HIV‐positive patients with anal squamous cell carcinomas.METHODS:We conducted a review based on our tumor registry from 1980 through 1999. We identified 73 patients with anal squamous cell carcinoma treated at the University of Texas Southwestern Medical Center affiliated hospitals; 23 were HIV positive (18 had AIDS). In the HIV‐positive group, 9 hadin situsquamous carcinomas and 14 had invasive squamous cell carcinomas. Data collected included age, CD4 count, treatment, complications, and survival; these data were analyzed by Student'st‐test.RESULTS:All patients were male. Those with squamous cell cancer of the anus were offered radiation therapy and chemotherapy. Beginning in 1998, all patients received highly active antiretroviral therapy before treatment. Seven of 14 anal squamous cell carcinoma patients had their therapy adjusted owing to toxicity. Morbidity included proctocolitis and diarrhea (n=2) requiring diversion (n=1), hemorrhagic cystitis (n=1), neutropenic fever (n=3), bone marrow suppression (n=1), and urethral stricture (n=1). Mean age was 42 years for anal squamous cell carcinoma patients and 36 years for squamous cell carcinomain situpatients (P=0.05). Mean CD4 count was 222 cells/ml in patients with infiltrating carcinoma and 200 in thein situpatients (P=NS). One‐year and five‐year mortality rates, respectively, were 40 percent and 80 percent for infiltrating carcinoma patients and 17 percent and 50 percent for thein situpatients. Both of thein situpatients who died had CD4 counts <20 cells/ml at diagnosis, whereas the rest had CD4 counts >100 cells/ml and are currently without anal disease. Mean CD4 count at diagnosis for all patients who died was 133 cells/ml, whereas for those surviving, it was 261 cells/ml (P=0.03). Eight (all with infiltrating carcinoma) of the 10 patients who died had persistent anal disease, but none had metastasis.CONCLUSION:HIV‐positive patients within situcarcinomas present at an earlier age than those with infiltrating lesions.In situpatients with CD4 counts as low as 105 cells/ml do well with local excision. A low CD4 count at diagnosis without highly active antiretroviral therapy predicts a poor prognosis. Because these patients appear to succumb to their HIV status and not the anal disease, anal squamous cell carcinoma should be included with cervical squamous cell carcinoma as an AIDS‐defining illness. HIV‐positive patients, particularly AIDS patients, with invasive anal cancers and without effective antiretroviral therapy obtain little benefit and significant toxicity from current radiation therapy and chemotherapy. Initiation of highly active antiretroviral therapy in HIV‐positive patients before radiation therapy and chemotherapy are begun may decrease toxicity and improve survival. Additional clinical trials are warranted to test this theory.