Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer

Abstract

SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index.

Immunopathogenesis of HPV-Associated Cancers and Prospects for Immunotherapy

“…In immunocompetent individuals, up to 90% of anogenital HPV infections are cleared within two years [ 36 , 37 , 38 ] and this is thought to be due to innate immunity as well as adaptive CD8 + T cell-mediated responses directed against viral early proteins [ 39 , 40 ]. Conversely, patients with impaired adaptive immunity, such as transplant recipients or HIV-patients, show higher prevalences of HPV infection and HPV-related diseases, further underlining the importance of immunosurveillance in HPV-associated carcinogenesis [ 8 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium

“…In 2003, the total number of NADCs exceeded the number of ADCs among people with HIV/AIDS [3]. Cancer deaths were responsible for more than one third of all deaths in HIV-infected patients [17], of which NADCs accounted for 26% of deaths, representing head and neck cancers (8%) and anal cancer (8%), among other malignancies [68]. As a result, NADCs currently comprise the majority of the global burden of cancer in HIV-infected populations, and represent an important public health concern.…”

“…Studies suggest that patients on HAART are at increased risk of acquiring opportunistic HPV infections and developing oropharyngeal [15,16], anal [17] and cervical cancers [18], compared to the general population. Oncogenic high-risk HPV16 is responsible for more than 60% of oropharyngeal carcinoma,~90% of tonsillar carcinomas [19], most cases of vulvar carcinoma [20], 90% of anal carcinoma [21] and penile cancers (less than 1% of all male cancers in the United States) with incidence rates that greatly vary across different regions of the world [21].…”

The role of pharmacologic modulation of autophagy on anal cancer development in an HPV mouse model of carcinogenesis

“…In addition to HPV vaccination, this may serve as another effective strategy for anal cancer prevention, especially in our high-risk patients (transplant, HIV, and immunocompromised patients, etc.) (Chin-Hong, 2016; Wang et al, 2017). Additional studies are required, utilizing more targeted drugs and/or genetic modulation of key autophagic proteins, in order to further elucidate the role of autophagy in anal carcinogenesis, and the role of autophagic modulation on anal cancer development.…”