The Facts about Oral HPV Infections: Head and neck cancers (HNCs), which rank as the seventh most prevalent type of tumors globally, presented a worrying 870,000 new cases and 440,000 deaths in 2020 alone. A considerable fraction of these cancers, especially oropharyngeal cancer (OPC), is linked to the Human papillomavirus (HPV) — a virus also notable for causing cervical cancer.
The Growing Concern over Oral HPV Infections OPC
In the United States, OPC has eclipsed cervical cancer, emerging as the foremost HPV-related cancer. Alarmingly, HPV-related OPC occurrences are still rising, especially amongst men, at an annual rate of 2.8%. Current research indicates that over 80% of OPC cases are due to HPV infections, with high-risk HPV types, including HPV-16, being the predominant causative agents.
The PROGRESS Study: Bridging Knowledge Gaps on Oral HPV
In light of the escalating OPC issue, researchers initiated the PROGRESS (Prevalence of Oral HPV Infection, a Global Assessment) study to delve deeper into the prevalence and diverse factors linked to oral HPV infections in the U.S. adult population. The groundbreaking study centered on individuals availing routine dental care services and offered insights into how different high-risk and low-risk HPV prevalence varied according to various sociodemographic and modifiable factors.
Oral HPV Infections Methodology
The cross-sectional PROGRESS study examined individuals between 18 to 60 years old, excluding those suspected or diagnosed with HNC. The approval process for this study met all ethical standards and adhered to guidelines for reporting observational studies.
Data for the study was assembled from March 2021 to April 2022, comprising inputs from participants across 21 states and 43 dental clinics, ensuring a diverse representation from urban to rural areas.
Survey and Health Assessments
Participants underwent a meticulous procedure involving oral rinse and gargle samples for HPV testing, coupled with detailed self-administered questionnaires to gather substantial information on sociodemographic elements, medical histories, and potential risk factors, including tobacco use and sexual behaviors.
Unveiled Facts and Further Inquiries
The study shed light on an essential area where data has been conspicuously scanty — the prevalence and type distribution of oral HPV infections. While it identified oral health as a potential risk factor for OPC, more definitive research is needed to affirm this connection.
The PROGRESS study stands as a vital initiative towards understanding the dynamics of oral HPV infections in the context of the burgeoning OPC crisis. As it uncovers critical data and associations, it paves the way for more focused research, potentially guiding future preventive strategies and public health policies to curb the increasing trend of HPV-related OPC in the community.
Understanding and addressing the spread of HPV-related OPC requires a collaborative effort, including regular screening and fostering awareness about the significant role of oral health. Let’s remain vigilant and informed as we await more insights from this pioneering study. Stay tuned for updates on this critical health issue.
Accepted for Publication: June 7, 2023.
Published Online: August 3, 2023. doi:10.1001/jamaoto.2023.1573
Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023 Giuliano AR et al. JAMA Otolaryngology–Head & Neck Surgery.
Corresponding Author: Marisa Felsher, PhD, MPH, Center for Observational and Real-World Evidence, Merck & Co, Inc, 126 E Lincoln Ave, Rahway, NJ 07065 (firstname.lastname@example.org).
Author Contributions: Dr Giuliano had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Giuliano, Felsher, Waterboer, Mirghani, Mehanna, Roberts, Lynam, Pedrós, Alemany, Morais, Pavón.
Acquisition, analysis, or interpretation of data: Giuliano, Felsher, Waterboer, Mehanna, Roberts, Chen, Lynam, Pedrós, Sanchez, Sirak, Surati, Alemany, Pavón.
Drafting of the manuscript: Giuliano, Felsher, Mirghani, Mehanna.
Critical review of the manuscript for important intellectual content: Giuliano, Felsher, Waterboer, Mirghani, Roberts, Chen, Lynam, Pedrós, Sanchez, Sirak, Surati, Alemany, Morais, Pavón.
Statistical analysis: Chen, Sanchez, Alemany.
Obtained funding: Roberts, Chen.
Administrative, technical, or material support: Felsher, Mehanna, Roberts, Lynam, Sirak, Surati, Pavón.
Supervision: Felsher, Waterboer, Mirghani, Roberts, Chen, Lynam, Alemany, Morais.
Other – Support on interpreting data and formatting the manuscript: Pedrós.
Conflict of Interest Disclosures: Dr Giuliano reported receiving grants to institution and personal fees (honoraria) from Merck Sharp & Dohme (MSD) during the conduct of the study; and serving on the Scientific Advisory Board and the Global Advisory Board for MSD. Dr Felsher reported receiving personal fees from Merck and receiving Merck stock as part of long-term incentive during the conduct of the study. Dr Waterboer reported receiving personal fees from MSD and serving on MSD advisory boards during the conduct of the study. Dr Mirghani reported receiving personal fees from MSD during the conduct of the study. Dr Mehanna reported receiving grants to institution from AstraZeneca and GSK PLC; personal fees (advisory boards) from Merck, MSD, Seagen, and Nanobiotix; other from Warwickshire Head Neck Clinic Ltd (shares and employment) and Docspert Health (shares) outside the submitted work. Dr Roberts reported being an employee and shareholder of and holding stock options from Merck during the conduct of the study and outside the submitted work. Dr Chen reported being an employee of Merck & Co, Inc, outside the submitted work. Ms Surati reported being an employee and shareholder of Merck & Co, Inc during the conduct of the study and outside the submitted work. Dr Alemany reported receiving grants to institution from Merck during the conduct of the study; and receiving grants to institution from MSD, Hologic, Seegene, GSK, and Roche outside the submitted work. Dr Morais reported receiving personal fees from MSD France during the conduct of the study. Dr Pavón reported receiving grants from MSD during the conduct of the study; nonfinancial support (free reagents to support a validation study not associated with the current study) from Seegene, Atila, Vitro, and Roche; and grants from MSD outside the submitted work. No other disclosures were reported.
Funding/Support: This study was funded and sponsored by Merck Sharp & Dohme, a subsidiary of Merck & Co (Rahway, NJ, USA).
Role of the Funder/Sponsor: In close collaboration with the external investigators, employees of Merck Sharp & Dohme, a subsidiary of Merck & Co (Rahway, NJ, USA), the sponsor and funder of the study, were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 PubMedGoogle ScholarCrossref
World Health Organization. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans: Human Papillomaviruses. World Health Organization; 2000.
Damgacioglu H, Sonawane K, Zhu Y, et al. Oropharyngeal cancer incidence and mortality trends in all 50 states in the US, 2001-2017. JAMA Otolaryngol Head Neck Surg. 2022;148(2):155-165. doi:10.1001/jamaoto.2021.3567
Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in human papillomavirus–associated cancers—United States, 1999–2015. MMWR Morb Mortal Wkly Rep. 2018;67(33):918-924. doi:10.15585/mmwr.mm6733a2 PubMedGoogle ScholarCrossref
Bouvard V, Baan R, Straif K, et al; WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens—part B: biological agents. Lancet Oncol. 2009;10(4):321-322. doi:10.1016/S1470-2045(09)70096-8 PubMedGoogle ScholarCrossref
Gillison ML, Alemany L, Snijders PJ, et al. Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis. Vaccine. 2012;30(suppl 5):F34-F54. doi:10.1016/j.vaccine.2012.05.070 PubMedGoogle ScholarCrossref
Wierzbicka M, Klussmann JP, San Giorgi MR, Wuerdemann N, Dikkers FG. Oral and laryngeal HPV infection: incidence, prevalence and risk factors, with special regard to concurrent infection in head, neck and genitals. Vaccine. 2021;39(17):2344-2350. doi:10.1016/j.vaccine.2021.03.047 PubMedGoogle ScholarCrossref
Ali A, Lassi ZS, Kapellas K, Jamieson L, Rumbold AR. A systematic review and meta-analysis of the association between periodontitis and oral high-risk human papillomavirus infection. J Public Health (Oxf). 2021;43(4):e610-e619. doi:10.1093/pubmed/fdaa156 PubMedGoogle ScholarCrossref
Morais E, Kothari S, Roberts C, et al. Oral human papillomavirus (HPV) and associated factors among healthy populations: the design of the PROGRESS (PRevalence of Oral hpv infection, a Global aSSessment) study. Contemp Clin Trials. 2022;115:106630. doi:10.1016/j.cct.2021.106630 PubMedGoogle ScholarCrossref
Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68(32):698-702. doi:10.15585/mmwr.mm6832a3PubMedGoogle ScholarCrossref
Geraets DT, Struijk L, Kleter B, et al. The original SPF10 LiPA25 algorithm is more sensitive and suitable for epidemiologic HPV research than the SPF10 INNO-LiPA Extra. J Virol Methods. 2015;215-216:22-29. doi:10.1016/j.jviromet.2015.01.001 PubMedGoogle ScholarCrossref
Kleter B, van Doorn L-J, ter Schegget J, et al. Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol. 1998;153(6):1731-1739. doi:10.1016/S0002-9440(10)65688-X PubMedGoogle ScholarCrossref
D’Souza G, Cullen K, Bowie J, Thorpe R, Fakhry C. Differences in oral sexual behaviors by gender, age, and race explain observed differences in prevalence of oral human papillomavirus infection. PLoS One. 2014;9(1):e86023. doi:10.1371/journal.pone.0086023 PubMedGoogle ScholarCrossref
Tsentemeidou A, Fyrmpas G, Stavrakas M, et al. Human papillomavirus vaccine to end oropharyngeal cancer: a systematic review and meta-analysis. Sex Transm Dis. 2021;48(9):700-707. doi:10.1097/OLQ.0000000000001405 PubMedGoogle ScholarCrossref
Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693-703. doi:10.1001/jama.2012.101
Gorphe P, Blanchard P, Garcia GCTE, et al. 2011-2021 Rising prevalence of HPV infection among oropharyngeal carcinoma in France. BMC Cancer. 2022;22(1):1000. doi:10.1186/s12885-022-10091-8 PubMedGoogle ScholarCrossref
Windon MJ, D’Souza G, Rettig EM, et al. Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. Cancer. 2018;124(14):2993-2999. doi:10.1002/cncr.31385 PubMedGoogle ScholarCrossref
Rettig EM, Zaidi M, Faraji F, et al. Oropharyngeal cancer is no longer a disease of younger patients and the prognostic advantage of human papillomavirus is attenuated among older patients: analysis of the National Cancer Database. Oral Oncol. 2018;83:147-153. doi:10.1016/j.oraloncology.2018.06.013 PubMedGoogle ScholarCrossref
de Souza MMA, Hartel G, Olsen CM, Whiteman DC, Antonsson A. Oral human papillomavirus (HPV) infection and HPV vaccination in an Australian cohort. Int J Cancer. 2023;153(2):417-426. doi:10.1002/ijc.34517 PubMedGoogle ScholarCrossref
Shigeishi H, Sugiyama M, Ohta K, et al. High HPV16 E6 viral load in the oral cavity is associated with an increased number of bacteria: a preliminary study. Biomed Rep. 2018;8(1):59-64. PubMedGoogle Scholar
Faraji F, Zaidi M, Fakhry C, Gaykalova DA. Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer. Microbes Infect. 2017;19(9-10):464-475. doi:10.1016/j.micinf.2017.06.001 PubMedGoogle ScholarCrossref
Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US adults: National Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc. 2018;149(7):576-588.e6. doi:10.1016/j.adaj.2018.04.023 PubMedGoogle ScholarCrossref
Kreimer AR, Pierce Campbell CM, Lin H-Y, et al. Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study. Lancet. 2013;382(9895):877-887. doi:10.1016/S0140-6736(13)60809-0 PubMedGoogle ScholarCrossref
Sohrabi A, Hajia M, Jamali F, Kharazi F. Is incidence of multiple HPV genotypes rising in genital infections? J Infect Public Health. 2017;10(6):730-733. doi:10.1016/j.jiph.2016.10.006 PubMedGoogle ScholarCrossref
Fischer DJ, O’Hayre M, Kusiak JW, Somerman MJ, Hill CV. Oral health disparities: a perspective from the National Institute of Dental and Craniofacial Research . Am J Public Health. 2017;107(S1):S36-S38. doi:10.2105/AJPH.2016.303622PubMedGoogle ScholarCrossref