Understanding Oral Human Papillomavirus (HPV) Infection, Acquisition, and Persistence in People Living with HIV (PLWH)

On this page

  1. Goal
  2. Background
  3. Gaps and Opportunities
  4. Specific Areas Of Interest
  5. References

September 2020

HIV/AIDS and Oral Health Research Program
Center for Clinical Research
Division of Extramural Research

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Goal

The goal of this initiative 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 the interrelationships between oral HPV infection and oral diseases in the context of HIV.

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Background

Between 2011 and 2014, it was estimated that approximately 7.3% of US adults aged 18-69 presented with any oral HPV DNA, 4% of whom had a high-risk oncogenic subtype.1 While the prevalence of oral HPV infection in the general population is rather low, people living with HIV have several risk factors that put them at increased risk for acquisition and persistence of infection, including sexual risk behaviors, HIV infection, lower CD4+ T cell counts, and use and extended duration on antiretroviral therapy.2

Previous research has found that people living with HIV have anywhere from a 2 to 4-fold increased risk for HPV-associated oropharyngeal squamous cell carcinomas as compared to HIV-negative individuals.2 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.5-7 Oral HPV persistence is reportedly associated with approximately 70% of oropharyngeal squamous cell carcinomas, and HPV Type 16 is the specific subtype associated with nearly 90% of HPV-positive oropharyngeal squamous cell carcinomas.3,4 Because screening for HPV-positive oropharyngeal carcinoma has not been supported by evidence,8 efforts have been focused on prevention via reduction of risk factors associated with oral HPV positivity and HPV vaccination.9 Further, Gardasil-9 was recently FDA approved for prevention of oropharyngeal carcinomas and other head and neck cancers using persistent oral HPV infection as an acceptable surrogate endpoint.10 Regardless, gaps in our knowledge base on oral HPV natural history and factors associated with persistent oral HPV infection hamper prevention efforts, especially in people living with HIV.

HPV is known to have an affinity to basal cells of the epithelium,11,12 and the gingival pocket is the only site in the oral mucosa where basal cells are normally exposed to the environment.12 Periodontal pocket formation is typically associated with a rapid proliferation and migration of the basal and supra-basal cells of the junctional epithelium and may offer a favorable site for replication of HPV.12 To support this biological hypothesis, previous observational studies have demonstrated associations between poor oral health, in particular periodontitis, and oral HPV infection and or oropharyngeal squamous cell carcinomas.13-15 Furthermore, immunologic and genetic data suggest a complex interaction between HIV and HPV.16 Given that people living with HIV present with an elevated risk for periodontal disease as well as HPV-related oral diseases, it is possible that oral HPV infection could further exacerbate the risk and severity of periodontitis and/or periodontal pockets may serve as a reservoir for persistent virus in this population.14,17

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Gaps and Opportunities

This initiative is timely, as the incidence of HPV-related oral diseases continues to increase, particularly oropharyngeal squamous cell carcinomas. It intends to address broad knowledge gaps related to our understanding of: a) the epidemiology of oral HPV infection in people living with HIV, and b) how HIV impacts oral HPV acquisition and persistence. Such information will better inform approaches for prevention of oral HPV infection and treatment/intervention of HPV-related oral diseases for people living with HIV.

This initiative builds upon the following two recent clinical and translational research initiatives:

  1. Oral Health in People Living with HIV and Additional Non-Communicable Diseases
  2. Engaging Dental Professionals to End the HIV Epidemic
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Specific Areas Of Interest

Examples of research areas that fall within the scope of this FOA include, but not limited to:

  • Understand the epidemiology of oral HPV acquisition and persistence in people living with HIV.
  • Assess the onset, extent, and progression of HPV-associated oral diseases in people living with HIV as compared to HIV negative individuals.
  • Elucidate the impact of HIV on oral HPV acquisition and persistence.
  • Determine the extent to which oral diseases and conditions may contribute to acquisition and persistence of oral HPV infection in people living with HIV.
  • Uncover the mechanisms and dynamics of HPV acquisition, persistence, and latency in cells within oropharyngeal tissue sites in people living with HIV.
  • Examine the impact of antiretroviral treatment on oral microbiome, HPV acquisition, its persistence, and HPV-associated oral diseases in people living with HIV.
  • Evaluate the successes of different treatment/intervention approaches for HPV-associated oral diseases in people living with HIV, including the impact of antiretroviral treatment on disease outcomes.
  • Study prevention approaches for oral HPV acquisition in people living with HIV by dental professionals or in dental settings.
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References

  1. McQuillan G, Kruszon-Moran D, Markowitz LE, Unger ER., Paulose-Ram R. Prevalence of HPV in adults aged 18–69: United States, 2011–2014. NCHS data brief, no 280. Hyattsville, MD: National Center for Health Statistics. 2017
  2. Cameron JE, Hagensee M. HPV-Associated Oropharyngeal Cancer in the HIV/AIDS Patient. Cancer Treat Res. 2019;177:131-181.
  3. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42.
  4. D’Souza, G., McNeel, TS, Fakhry, C. Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer. Ann Oncol. 2017 Dec 1;28(12):3065-3069.
  5. Zavras AI, Shanmugham JR. Measurement and Distribution of Oral Cancer. In: Mascarenhas AK, Okunseri C, Dye BA, eds. Burt and Eklund’s Dentistry, Dental Practice, and the Community. 7th ed. St Louis, MO: Elsevier; 2020:189-201
  6. Ellington TD, Henley SJ, Senkomago V, et al. Trends in Incidence of Cancers of the Oral Cavity and Pharynx - United States 2007-2016. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):433-438
  7. Centers for Disease Control and Prevention. HPV-Associated Cancer Statistics. Available at: https://www.cdc.gov/cancer/hpv/statistics/#:~:text=Cervical%20cancer%20is%20the%20most,the%20most%20common%20among%20men
  8. Day AT, Fakhry C, Tiro JA, et al. Considerations in Human Papillomavirus-Associated Oropharyngeal Cancer Screening: A Review. JAMA Otolaryngol Head Neck Surg. 2020;146(7):656-64
  9. Centers for Disease Control and Prevention. HPV and Oropharyngeal Cancer. Available at: https://www.cdc.gov/cancer/hpv/basic_info/hpv_oropharyngeal.htm
  10. U.S. Food & Drug Administration. Vaccine: Gardasil 9. Available at: https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9
  11. Pullos AN, Castilho RM, Squarize CH. HPV Infection of the Head and Neck Region and Its Stem Cells. J Dent Res. 2015;94(11):1532-43
  12. Shipilova A, Dayakar MM, Gupta D. High risk human papillomavirus in the periodontium: A case control study. J Indian Soc Periodontol. 2017;21(5):380-5
  13. McDaniel JT, Davis JM, McDermott RJ, et al. Predicted prevalence of oral human papillomavirus (HPV) by periodontitis status and HPV vaccination status. J Public Health Dent. 2020:80(2):132-9
  14. Tezal M, Sullivan Nasca M, Stoler DL, et al. Chronic periodontitis-human papillomavirus synergy in base of tongue cancers. Arch Otolaryngol Head Neck Surg. 2009;135(4):391-6
  15. Shigeishi H, Sugiyamab M. Risk Factors for Oral Human Papillomavirus Infection in Healthy Individuals: A Systematic Review and Meta-Analysis. J Clin Med Res. 2016 Oct; 8(10): 721–729
  16. Denny LA, Franceschi S, de Sanjose S, et al. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine. 2012;30(Suppl 5):F168-74
  17. Pólvora TLS, Nobre ÁVV, Tirapelli C, et al. Relationship Between Human Immunodeficiency Virus (HIV-1) Infection and Chronic Periodontitis. Expert Rev Clin Immunol. 2018 Apr;14(4):315-327
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Last Reviewed
April 2024