As a result of the extension of life span produced by increasing access to combined antiretroviral therapy, people living with HIV/AIDS (PLWH) face new challenges from comorbidities. Although advances in medical care for HIV infection have dramatically reduced opportunistic infections and AIDS‐defining cancers, some non‐AIDS‐defining cancers (NADC) and specific oral diseases such as periodontitis and salivary gland disease are now more prevalent. Cancer prevention is, therefore, a priority issue in care of PLWH, stressing both restoration of immune function and reduction of non‐HIV cancer risk factors (tobacco in all its forms; areca nut; heavy alcohol consumption; diets lacking antioxidant vitamins and minerals; and oncogenic virus infections) through specific interventions, especially tobacco and areca nut cessation and alcohol moderation. Detection of oral high‐risk human papillomaviruses (HR‐HPV) and the universal preventive HPV vaccination among PLWH should be promoted to reduce the malignancy burden, along with routine oral examinations which remain the cheapest, most reliable, most reproducible, and non‐invasive tool to identify suspicious lesions. Also, considerations of oral inflammation and periodontal health are important to replication and gene expression of viruses in the mouth. Considering that a key risk factor for this scenario is the presence of oncogenic virus infection such as several members of the human herpesvirus and human papillomavirus families, here we analyze the variables involved in the seeming increase in comorbidities in PLWH.