Oropharyngeal cancer, affecting the back of the mouth and the throat, has been rising in people with and without HIV in recent decades. It is often caused by human papillomavirus (HPV), a common sexually transmitted infection. A recent analysis looked at incidence and risk factors among 135,359 HIV-positive people in North America. A total of 254 were diagnosed with oropharyngeal cancer between 2000 and 2021, with the incidence rate more than tripling over time. People ages 50 to 59 had the highest incidence rate, while incidence was negligible among those under 40. Men were about three times more likely to be diagnosed than women, and heterosexual men had a higher incidence than gay and bisexual men. People with oral cancer had a lower nadir (lowest-ever) CD4 T-cell count and were more likely to smoke, drink heavily and inject drugs. Given their age, most participants were ineligible when the HPV vaccine was first recommended for adolescents and young adults; future studies will show whether oral cancer declines in younger cohorts with higher vaccination rates.