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HPV types Table 6 presents the most common anatomic sites and symptoms of HPV-positive cancers arising in the oropharynx. Table 6: HPV-Positive Oropharyngeal Cancer Sites and Symptoms Anatomic Site in the Oropharynx Cancer Symptoms Base of the tongue • Pain • Trouble swallowing • Weight loss • Ear pain • Limited ability to open mouth due to muscle spasms • Reduced range of motion for tongue Tonsillar region Most common location for a primary tumor of the oropharynx May appear as areas of • Pain • Trouble swallowing • Weight loss • Ear pain • Mass in neck

Prevalence and incidence Based on SEER (Surveillance, Epidemiology, and End Results Program) the estimated number of new cases (incidence) of oral cavity oropharyngeal cancer for 2022 is 11.5 per 100,000 men and women per year with the death rate at 2.5 per 100,000 men and women per year (National Cancer Institute, n.d.b). An estimated 68.0% of individuals diagnosed with this cancer will survive 5 years (NCI, n.d.b.). Between the years of 1999-2015 a dramatic shift occurred in the number of HPV-associated cervical and oropharyngeal malignancies in the United States. In 1999 there were 13,125 HPV-associated cervical malignancies compared to 9,375 HPV-associated oropharyngeal malignancies. By 2015 the HPV-associated oropharyngeal malignancies outnumbered the cervical malignancies by 18,917 to 11,788 with 82% (15,479) of these oropharyngeal malignancies afflicting males (Roos, 2018). The HPV accounts for 71% of all (OPSCC) cases in the United States with the HPV-16 strain found in 85-96% of these cases with 4.62 per 100,000 HPV-positive cases compared to 1.82 per 100,000 (OPSCC) which are HPV-negative (Lechner et al., 2022). Evidence points to HPV infection as the major cause for rising rates of oral cancer cases in the United States (National Comprehensive Cancer Network, 2018). Signs and symptoms Patients with HPV-related oral cancer can present with variable symptoms such as a mass in the neck, a unilateral earache, numbness in the mouth or lips a protracted sore throat or hoarseness of the voice, dysphagia, asymmetry of the tonsils (If present) or an intraoral sore or ulcer that does not heal (The Oral Cancer Foundation, 2022). Because these cancers develop in the oropharynx, patients typically do not notice early symptoms (CDC, 2022c). Additionally, patients who are unaware of the differing risk factors for HPV-positive versus HPV-negative oropharyngeal cancers may perceive their risk for this cancer as low. Compounding this, the anatomic location of HPV-positive cancers, in the oropharyngeal area, makes detection difficult. This difficulty is further compounded by the absence of reliable screening methods. Prevention – stopping transmission of the virus – is therefore the key to combatting HPV-positive oropharyngeal cancers (UCSF, 2019). See Table 6 for oropharyngeal cancer symptoms by anatomic site.

swelling, inflammation, or a superficial spreading lesion

Soft palate (including uvula)

• Painless ulcer that becomes painful over time • Bleeding • Changes in speech/voice • Difficulty swallowing • Limited ability to open mouth • Mass in neck

Pharyngeal walls

• Pain • Bleeding

• Weight loss • Mass in neck

Note . Adapted from “Palate Cancer,” by Cedars-Sinai, n.d., retrieved from https://www.cedars-sinai.edu/Patients/Health- Conditions/Palate-Cancer.aspx; Cleveland Clinic. Oropharyngeal Human Papillomavirus (HPV) infection. Last reviewed July 11, 2022. https://myclevelanclinic.org>health>diseases>150...; Lechner Matt, Liu Jacklyn, Masterson Liam and Fenton, Tim R. HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 19, 306- 327 (2022). https://www.nature.com>...>reviewarticles; Gorphe Philppe, Calsse Marion, Ammari Samy, et.al. Patterns of disease events and causes of death in patients with HPV-positive versus HPV-negative oropharyngeal carcinoma. Radiotherapy and Oncology. 168 (January 2022) 40-45. https://www.sciencedirect. com>science>article>pii; American Dental Association. Cancer (Head and Neck) Department of Scientific Information, Evidence Synthesis and Translation Research, ADA Science and Research Institute, LLC. Last updated: September 30, 2022. Diagnosing the cancer As previously stated, studies have shown that patients with HPV-positive oral cancer are less likely to have the traditional risk factors of tobacco and alcohol use (Tillman, 2019). For this reason, along with an updated health history, all dental patients should have a screening for oral and pharyngeal cancer at every dental visit (American Dental Association, 2019; American Dental Association 2022; Rehan, 2017). Patients with symptoms (e.g., a non-healing ulcer or other changes in the mucosa) that persist longer than 2 weeks merit further investigation, such as a biopsy

or referral to a specialist (Al-Eryani, 2022). HPV detection requires the combined assessment of p16 expression by immunohistochemistry (IHC) and the presence of viral DNA by polymerase chain reaction (PCR); therefore, diagnosing the cancer as HPV-positive or HPV-negative will likely occur at the time of surgical biopsy or resection Gougousis, et al., 2021; Ducatman, 2018). The HPV status of the tumor is useful for directing treatment regimens. Table 7 provides a list of chairside tests for detecting oral cancer.

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