Human papillomavirus (HPV) causes a growing majority of oropharyngeal cancers (OPCs) in developed countries. The etiologic relationship between HPV and OPC was described relatively recently and our understanding of the disease continues to evolve, such that knowledge gaps persist among both providers and patients. Clinicians currently positioned to discuss oral HPV infection and HPV-positive OPC (HPV-OPC) include primary care providers, otolaryngologists, oral health professionals, and oncologists. It is critical that patients receive counseling based on the best available evidence, especially in context of the unique distress associated with any cancer caused by a sexually transmitted infection (STI).

Studies suggest patients are highly anxious at the initial diagnosis of HPV-OPC,¹ with concerns including cancer-related mortality and anticipated decrements in quality of life. Half of patients report concerns about intimacy and HPV transmission (Figure 1),² and both patients and partners can experience feelings of guilt.³ Some common patient questions are addressed here.

What does HPV mean for prognosis and treatment?It is important for providers to communicate that most HPV-OPCs are highly treatable with 85-90% 2-year survival, on average. This is a dramatic improvement compared with HPV-unrelated OPC, for which 2-year survival is closer to 65% overall.* Currently, treatment for HPV-OPC remains the same as for HPV-negative OPC, and includes one or a combination of surgery, radiation and chemotherapy. However, there are multiple clinical trials underway to determine whether the intensity of treatment may be reduced, thereby decreasing side effects while maintaining excellent survival.

How and why did I get HPV-OPC?
When addressing HPV, it should be emphasized that exposure is very common. Over 80% of U.S. individuals show evidence of exposure by age 45, such that infection does not necessarily reflect promiscuity. Though less prevalent than anogenital infection, oral HPV is still detected in approximately 7% of the general population, with a 3.7% prevalence of the high-risk HPV types that cause cancer.⁴ Oral HPV is more likely among men, smokers, and individuals with a greater number of oral sexual partners (Figure 2).⁵ Although most infections clear, in rare instances persistent infection with high-risk strains can eventually cause OPC; this likely occurs over the course of decades. Factors that cause some persistent infections to become cancer are not well understood. Importantly, a diagnosis of HPV-OPC likely reflects an exposure to HPV from many years earlier, and therefore does not insinuate infidelity.

* These percentages were calculated from a contemporary database of 37,000 OPC cases with known HPV status in the United States (the National Cancer Database).

Prevalence of high concern among patients with human papillomavirus-positive oropharyngeal cancer regarding disease-related issues at diagnosis. Adapted from, Oral Oncology, 95, Windon et. al., “Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment”, 11-15, Copyright (2019), with permission from Elsevier.

For patients with current partners, there is no evidence to recommend changes in sexual practice as partners would have already been exposed to any HPV infections. Partners of HPV-OPC patients do not appear to have a significantly increased risk for oral HPV infection; indeed, the prevalence of oral HPV among partners is similar to that of the general population. With new partners, patients should be encouraged to follow usual safe sex practices to prevent transmitting any STI. Barrier use during oral sex has been associated with decreased oral HPV infection, but it is not known whether this lowers the risk of HPV-OPC. There is no evidence to support HPV transmission by casual contact such as a kiss on the cheek.

Infographic describing personal risk of oral infection with human papillomavirus type 16 (HPV16), the high-risk type implicated in the vast majority of oropharyngeal cancers, and any high-risk HPV type including HPV16 (OncHPV), among the general US population. Percentages describe the prevalence of infection according to risk factor profiles derived from National Health and Nutrition Examination Survey (NHANES) data collected between 2009 and 2014. Reprinted from Annals of Oncology, 28, D’Souza et. al., “Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer, p3065-3069, Copyright (2017), with permission from Oxford University Press.

Is HPV-OPC preventable?
Initial data shows a reduced prevalence of oral HPV infection among those who received the HPV vaccine,⁶ and it is widely believed vaccination will reduce the incidence of HPV-OPC. The U.S. FDA has approved Gardasil 9 for men and women ages 9-45, and family members and partners within this age range should be encouraged to receive the vaccine. Though screening for oral HPV and for HPV-OPC is not recommended outside of clinical trials,⁷ patients and partners should follow cervical HPV screening guidelines.

Counseling about HPV-OPC should address patients’ concerns regarding survival, etiology, transmission, prevention and screening. Key points are summarized in Table 1.

DISCLOSUREThe authors declare nothing to disclose.

Key points for counseling patients with human papillomavirus-positive oropharyngeal cancer.

ARTICLES INCLUDED IN THE HPW SPECIAL ISSUE ON HPV IN OROPHARYNGEAL CANCER:

AR Kreimer, T Waterboer. Screening for HPV-Driven Oropharyngeal Cancer

M Taberna, R Mesia, RL Ferris. Clinical management of HPV-related recurrent/metastatic (R/M) oropharyngeal cancer patients

S Huang. Oropharyngeal Carcinomas: the UICC/AJCC TNM Staging System, 8th Edition

G D’Souza, A Chaturvedi, E Bigelow. Natural history, from oral HPV infection to HPV related oropharyngeal cancer

References

1. D'Souza G, Zhang Y, Merritt S, et al. Patient experience and anxiety during and after treatment for an HPV-related oropharyngeal cancer. Oral Oncology 2016;60(2016):90-95. Available from: https://pubmed.ncbi.nlm.nih.gov/27531878/

2. Windon MJ, Fakhry C, Faraji F, et al. Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment. Oral Oncology 2019;95:11-15. Available from: https://pubmed.ncbi.nlm.nih.gov/31345377/

3. Taberna M, Inglehart RC, Pickard RKL, et al. Significant changes in sexual behavior after a diagnosis of human papillomavirus-positive and human papillomavirus-negative oral cancer. Cancer 2017;123(7):1156-1165. Available from: https://pubmed.ncbi.nlm.nih.gov/28195638/

4. Gillison ML, Broutian T, Pickard RKL, et al. Prevalence of Oral HPV Infection in the United States, 2009-2010. JAMA 2012;307(7):693-693. Available from: https://pubmed.ncbi.nlm.nih.gov/22282321/

5. D'Souza G, McNeel TS, Fakhry C. Understanding personal risk of oropharyngeal cancer: Risk-groups for oncogenic oral HPV infection and oropharyngeal cancer. Annals of Oncology 2017;28(12):3065-3069. Available from: https://pubmed.ncbi.nlm.nih.gov/29059337/

6. Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the United States. Journal of Clinical Oncology 2018;36(3):262-267. Available from: https://pubmed.ncbi.nlm.nih.gov/29182497/

7. Kreimer AR, Shiels MS, Fakhry C, et al. Screening for human papillomavirus-driven oropharyngeal cancer: Considerations for feasibility and strategies for research. Cancer 2018;124(9):1859-1866. Available from: https://pubmed.ncbi.nlm.nih.gov/29499070/