TOPLINE

Longer use of antiretroviral therapy (ART) was not associated with a lower risk for anogenital cancer in people living with HIV (PLWH). The risk was higher with a longer treatment duration and was highest among those treated for 10 years or more compared with those without HIV infection.

METHODOLOGY

• Researchers conducted a case-cohort study that emulated a target trial to assess whether a longer duration of ART was associated with the risk for anogenital cancer in PLWH vs those without HIV infection.
• The analysis included 1045 participants aged 30-65 years in Botswana who were diagnosed with cervical, vulvar, anal, or penile cancer between 2013 and 2018 and compared them with 13,267 randomly sampled residents of 30 rural and peri-urban communities.
• Researchers interviewed participants, offered them HIV testing, and checked their medical records. CD4 counts came from patient-kept records and laboratory databases, and cancer types were determined from pathology and clinical records.
• PLWH were grouped according to ART duration (none, less than 5 years, 5-9 years, or 10 years or more) and compared with participants without HIV infection. Those treated for less than 9 months were classified as untreated.

TAKEAWAY

• Among participants with newly diagnosed anogenital cancer, 79% had HIV infection, and 86% of them were receiving ART. The cases included 792 cervical, 106 vulvar, 80 anal, and 67 penile cancers.
• The relative risk (RR) for any anogenital cancer among PLWH was 4.6 with no ART, 4.0 with less than 5 years of therapy, 4.6 with 5-9 years of therapy, and 7.4 with 10 or more years of therapy, compared with participants without HIV infection. The risk was higher with a longer therapy duration (P = .001).
• Across all cancer sites, the risk was highest among those treated for 10 years or more: PLWH who had received ART for 10 years or more had RRs of 4.4 for cervical cancer, 35.7 for vulvar cancer, 14.9 for anal cancer, and 102 for penile cancer.
• A history of advanced HIV disease was associated with a higher risk for anogenital cancer, particularly among PLWH not yet receiving ART. For cervical cancer among women with HIV infection, this excess risk diminished with longer therapy and was no longer evident after more than 5 years (P = .027 for trend).

IN PRACTICE

"The risk of cervical, anal, vulvar, and penile cancers appeared to increase with a longer duration of HIV infection despite ART, potentially related to earlier periods of immunocompromise and cumulative exposure to HIV-related immune dysfunction," the authors wrote.

"While expanding childhood HPV [human papillomavirus] vaccination to protect future generations, a concurrent expansion of detection and treatment of anogenital dysplasia in PWH [people with HIV] is needed," they added.

SOURCE

The study was led by Maanasa Mendu, Botswana Harvard Health Partnership, Gaborone, Botswana. It was published online on September 25, 2026, in Clinical Infectious Diseases.

LIMITATIONS

Time since HIV diagnosis was closely related to ART duration; therefore, the study could not separate their individual effects. PLWH who had been on therapy for 10 years or more had advanced HIV disease when they began treatment, and the analysis may not have fully adjusted for this factor. Broader cervical precancer screening, especially for PLWH, may have prevented some cervical cancers and lowered the observed risk in the long-term therapy group.

DISCLOSURES

The study was funded by the National Cancer Institute and the National Institute of Allergy and Infectious Diseases, both part of the National Institutes of Health. One author disclosed receiving payments from Roche/Genentech, Novartis, and MSD Oncology and travel support from Roche and MSD Oncology.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.