Oropharyngeal cancer is becoming more common in heterosexual men with HIV

Cancer in the back of the mouth or throat (oropharyngeal cancer) is no longer a rare cancer in some groups of people with HIV, especially heterosexual men, a large North American study reported at the Conference on Retroviruses and Opportunistic Infections (CROI 2026) in Denver, US on Monday.

Oropharyngeal cancers occur in the base of the tongue, the soft palate and the tonsil area. The American Cancer Society estimates that approximately 60,000 people in the United States will be diagnosed with a cancer of the mouth or throat in 2026. The most common causes are smoking, alcohol or the cancer-causing strains of human papillomavirus (especially HPV-16).

The likelihood of being diagnosed with oropharyngeal cancer increases after the age of 50, although oropharyngeal cancer is uncommon compared to lung, bowel, breast and prostate cancer in the general population.

In 2025, Dr Antonio Bandala-Jacques and colleagues at the Johns Hopkins Bloomberg School of Public Health in Baltimore published a meta-analysis of studies on the incidence of oropharyngeal cancer in the United States. As well as finding that incidence in the general population has risen over the past 20 years, they reported that the incidence rate was highest in men living with HIV (35 per 100,000 person-years of follow-up). Furthermore, the incidence of oropharyngeal cancer in men was higher than the incidence of cervical cancer (also caused by HPV) in women.  

At CROI 2026, Bandala-Jacques presented findings from an analysis of oropharyngeal cancer risk factors and incidence between 2000 and 2020 in 135,356 people with HIV enrolled in cohorts contributing to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which brings together data from 21 cohorts.

Using cancer registries, the researchers looked for confirmed diagnoses of oropharyngeal squamous cell cancer in cohort members and found 254 cases. The incidence rate rose from 15.7 per 100,000 person-years (PY) of follow-up between 2000 and 2002, to 42.3 per 100,000 PY between 2018 and 2020.

The incidence was highest in the 50-59 age group (49.2 per 100,000 PY) and lowest in the under-40s (2.9 per 100,000 PY).

Women with HIV were 50% less likely to be diagnosed with oropharyngeal cancer than men (31.4 per 100,000 PY in men vs 10.9 per 100,000 PY in women).

Incidence was highest in heterosexual men and people who inject drugs, lower in gay and bisexual men, and lowest in heterosexual women. Compared to gay and bisexual men, heterosexual women had a 50% lower likelihood of being diagnosed with oropharyngeal cancer, while heterosexual men had a 50% higher likelihood of diagnosis.

Less severe immunosuppression was associated with a lower likelihood of oropharyngeal cancer. A lowest-ever CD4 count between 200 and 499 was associated with a 30% reduction in the risk of oropharyngeal cancer compared to a lowest-ever count below 200; a lowest-ever CD4 count above 500 was associated with a 50% reduction in risk.

Histories of smoking or alcohol abuse each increased the risk of oropharyngeal cancer by 30%.

“Oropharyngeal cancer is no longer a rare cancer in some people living with HIV,” Dr Bandala-Jacques concluded.

He said that the leading theory for the higher rate of oropharyngeal cancer in people living with HIV was greater persistence of HPV in people with HIV. A greater likelihood of HPV transfer from female genitalia than male genitalia during oral sex may explain the higher rate of oropharyngeal cancer in heterosexual men. Slower clearance of oral HPV infection in men may be a contributing factor, other Johns Hopkins University researchers have suggested.

Another explanation is that genital infection with HPV does not result in high levels of antibodies to HPV. In contrast, anal transmission has been shown to produce high levels of antibodies in gay and bisexual men that may protect against oropharyngeal infection, commented Professor Tim Wilkin of the University of California, San Diego.

The study was unable to assess the proportion of cancers that were HPV-related or the HPV vaccination status of participants due to insufficient data. Dr Bandala-Jacques said that, with a median age of 50 at cohort entry, few participants were likely to have been vaccinated.

The study findings suggest that heterosexual men with HIV are in particular need of regular screening for oropharyngeal cancer, especially those with a history of smoking, alcohol abuse or immunosuppression.

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