Human Papillomavirus-Associated Head and Neck Cancer

Juan C. Nogues, BS; Scott Fassas, MD; Collin Mulcahy, MD; Philip E. Zapanta, MD

J Am Board Fam Med. 2021;34(4):832-837.

Epidemiology

OPSCC has historically been a disease affecting older male smokers. As the rates of tobacco consumption have declined in the United States, there has been a decreased incidence of many head and neck cancers. HPV-related head and neck cancers, however, have not followed this overall trend, with multiple sources demonstrating a rise in incidence over the last 2 decades.^[4–6] Specifically, the percentage of HPV-related cancers has jumped from 41%, before 2000, to 72% between 2005 and 2009 (Figure 2).^[7] While previous literature estimated the incidence of HPV-related OPSCC would surpass HPV-related cervical cancer by 2020,^[8,9] data collected by the Centers for Disease Control and Prevention (CDC) have suggested that the total incidence has already surpassed HPV-related cervical cancer well before this time frame.^[2]

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Figure 2.

Human Papillomavirus (HPV) Prevalence Among Patients With Oropharyngeal Cancer as Reported in A Systematic Review and Meta-Analysis of Studies Published Between 1966 and 2010.⁷

While marijuana exposure has been shown to be an independent risk factor for the development of HPV-positive head and neck cancer,^[10] the primary reason for the increase in OPSCC is related to an overall rise in high-risk sexual practices. More than 90% of oral HPV infections are related to sexual activity, with oral sex being the largest predisposing factor.^[11,12] Furthermore, patients impacted by HPV-positive OPSCC are generally younger than their HPV-negative counterparts and overwhelmingly white males—typically between the ages of 40 and 55.^[13]

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Table 1. Proposed HPV Screening Tools ¹²
Screening Tool	Concept	Limitation
Oral HPV screening	Sample patient's saliva and test for high-risk HPV viral DNA	Although this can detect the presence of HPV DNA, the majority of individuals will go on to clear the virus without progressing to carcinoma
HPV serology	Asses serum levels of antibodies to high-risk HPV strands	Serum antibody levels represent the cumulative exposure to HPV but are not specific to exposure at a particular anatomic site (oropharynx, cervix, etc.) and do not reflect expression of HPV-related oncoproteins E6 and E7, which are necessary for carcinogenesis
Transcervical ultrasound	Ultrasound of the head and neck can be used to assess individuals with neck masses or those who are found to be at high risk via other screening methods. It may help detect small tumors in earlier stages and improve morbidity	Although ultrasound is relatively inexpensive and can be done quickly in the office, it is not practical for universal screening and relies on either the symptom of a neck mass or other screening method to prescreen high-risk individuals
Mucosal imaging	Direct visualization of subclinical lesions via endoscopy	There are no identifiable premalignant lesions, and as with the limitations of ultrasound, there needs to be a prescreening method to identify high-risk individuals before subjecting them to this more invasive procedure. Additionally, many of these tumors arise from tonsillar crypts and cannot be easily identified on surface-level examination