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.

Screening and Presentation

Unlike cervical cancer, which uses Papanicolaou cytology screening to assess precancerous lesions of the cervix, there are currently no practical screening tools available for HPV-positive OPSCC screening.^[12] Several techniques are under investigation, but each has limitations that preclude its use for population-level screening (Table 1). Furthermore, validated sexual history screening questionnaires have not been developed to capture patients most at risk.

Without a validated screening test or questionnaire to detect patients with or most at risk for HPV-positive OPSCC, it is imperative that first-line health care providers (PCPs and dentists) remain cognizant of the current epidemiologic factors discussed above. This information, coupled with knowledge and awareness of common clinical presentations, can be greatly beneficial to patients. A recent retrospective analysis of 207 patients with OPSCC found that patients with HPV-positive OPSCC were most likely to present with a neck mass (56%), sore throat (11%), or oral mass (11%).^[14] Furthermore most HPV-positive patients in this study presented at a tumor, node, metastasis stage of IVa (57%), with the tonsil (60%) and base of tongue (40%) being the most common primary tumor site.^[14]

If a patient presents to the office with a history suspicious for OPSCC, it is recommended that providers conduct a formal head and neck examination that includes inspection of the oral cavity, palatine tonsils, base of tongue, and cervical lymph nodes. An external light source and tongue blade are important for optimum visualization of the oral cavity and oropharynx for asymmetries or lesions. A mirror may be used to inspect the vallecula. Thorough palpation of the tonsillar fossae and tongue base can identify induration, ulceration, or swelling.^[15]

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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