NIH – Understanding Oral Human Papillomavirus (HPV) Infection, Acquisition, and Persistence in People Living with HIV (R01 Clinical Trial Not Allowed)

July 2, 2021 by


The purpose of this Funding Opportunity Announcement (FOA) is to solicit research to better understand the epidemiology and biology of oral human papillomavirus (HPV) infection, its acquisition and persistence, in people living with HIV and elucidate the initial mechanisms related to HPV-associated oral and orophrayngeal cancers and warts in the context of HIV. The FOA intends to address broad knowledge gaps related to biological, immunogenetic, clinical, and socio-behavioral factors and mechanisms for oral HPV co-infection and persistence in the oral cavity and oropharynx of HIV-seropositive individuals.


HPV has been identified as an etiologic agent of oral warts and head and neck squamous cell cancers, primarily involving the oropharynx. Oropharyngeal squamous cell carcinomas are among the most common HPV-related cancers in the United States, and the incidence of HPV-related oropharyngeal squamous cell carcinomas has shown a significant increase in the United States over the last decade. Based on data from 2013 to 2017, estimated 14,000 of approximately 45,300 new cases of HPV-associated cancers occurred in the US each year were in the area of oropharynx.

Most initial oral HPV infections, within the general population, are asymptomatic and typically go unnoticed. However, people living with HIV are at increased risk of oral HPV infection, persistence, and HIV-associated oral complications. Non-oncogenic or “low-risk” HPV genotypes, in particular HPV-32, are commonly found in oral warts, and HPV-16, one of the “high-risk” or oncogenic HPV genotypes, is detected in more than 90% of oropharyngeal cancers. Due to reasons that remain unknown, people living with HIV suffer HPV-associated oral warts, benign oral pathologies not often seen in the general population, and have anywhere from a 2 to 4-fold increased risk for HPV-associated oropharyngeal squamous cell carcinomas as compared to HIV-negative individuals.

HPV is known to have an affinity to basal cells of the epithelium, and the gingival pocket is likely the only site in the oral mucosa where basal cells are normally exposed to the environment. Another theorized entry point for HPV may be the exposed basement membrane of tonsiller or lingual crypts, where the epithelial layer is discontinuous to allow for lymphoid cell lineages to travel from the stroma to the epithelium. One possible issue for people living with HIV or people at risk for HIV that are on pre-exposure prophylaxis includes the potential toxicity of ART on oral epithelium leading to a weakening of local immunity against HPV. Additional studies in other HPV-associated tumor types suggest a complex genetic and immunologic interaction between HIV and HPV. In the United States, over half of the people living with HIV are aged 50 and older. Aging-related inflammatory comorbidities could directly or indirectly modify the process and outcome of oral HPV co-infection and its persistence.

Key Dates:

Open Date (Earliest Submission Date): October 18, 2021
Letter of Intent Due Date(s): October 18, 2021
Application Due Date: November 19, 2021

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Filed Under: Funding Opportunities