Cases in Tonsil Disease: From the Routine to the Serious

Gordon H. Sun, MD, MS


May 23, 2017

A Growing Cause of Head and Neck Cancer

Head and neck cancers, 90% of which are squamous cell carcinomas (SCCs), are the ninth most common malignancy worldwide.[36] In the United States, approximately 45,000 new cases and 8500 deaths are attributed to oral cavity and oropharyngeal cancers per year.[37] The incidence of oral cavity cancer has declined over the past few decades, likely as a result of public health efforts that have reduced the prevalence of tobacco and alcohol use.[38] However, the proportion of OPSCC cases potentially attributable to HPV infection has dramatically risen since at least the 1970s.[38,39,40]

HPV is the most common sexually transmitted infection in the United States and is a major US public health concern. Data from the 2011-2014 National Health and Nutrition Examination Survey showed a genital viral prevalence of 42.5% and an oral viral prevalence of 7.3% among adults aged 18-59 years.[41] HPV was estimated to account for about 16% of US cases of HPV-positive OPSCC in the early 1980s, compared with 60%-80% in more contemporary studies.[42,43,44]

A high proportion (73%-87%) of all HPV-positive head and neck cancers contain HPV subtype 16,[45,46] whereas 87%-96% of HPV-positive OPSCC cases are associated with HPV 16.[45,47] Other high-risk HPV subtypes, such as 18 and 33, also contribute to OPSCC disease burden, but in far lower proportions.[45] The oropharynx has surpassed the cervix as the most common site of HPV-related cancer in Americans.[48] HPV seropositivity and smoking are independent, additive risk factors for oropharyngeal cancer.[49]

In contrast to the so-called "traditional" head and neck cancer patient (older and with significant tobacco and alcohol exposure), the "new" head and neck cancer patient has been described as relatively younger (fifth and sixth decades at the time of presentation), primarily male, with minimal or no exposure to tobacco and alcohol but often increased numbers of sexual encounters, specifically involving oral sex.[50] HPV-positive OPSCC patients are typically of higher socioeconomic status than those with HPV-negative disease, and white OPSCC patients had higher rates of HPV 16 and 18 infection compared with black and Asian patients.[51,52] A single-institution study by McIlwain and colleagues[53] found that the five most common chief complaints among 71 patients with HPV-positive OPSCC were neck mass (51%), sore throat (28%), visualized mass (14%), dysphagia (10%), and globus sensation (10%). HPV-positive OPSCC is found most commonly in the palatine tonsils or tongue base and has a high rate of cervical metastasis.[54]

HPV-positive OPSCC is associated with a significantly improved prognosis compared with HPV-negative OPSCC. Numerous studies have demonstrated higher survival rates in HPV-positive patients, and this survival advantage persists in cases treated across the United States, Europe, Australia, and Brazil.[55,56,57,58] The better prognosis of HPV-positive OPSCC is believed to be related to the high responsiveness of these cancers to surgery, radiation therapy, and chemotherapy, as well as the generally more robust baseline health of such patients—younger, nonsmoking, and with few comorbid conditions.[59,60] Favorable initial responses to treatment notwithstanding, up to 30% of patients with HPV-positive head and neck SCC experience recurrent disease.[51]

Three types of HPV vaccines, all of which target the high-risk HPV 16 and 18 subtypes, currently exist—2-valent, 4-valent, and 9-valent.[61] Although HPV vaccines appear to be effective in preventing anogenital HPV infections, uptake of these vaccines among US adolescents has remained relatively low.[51,62,63] There also has been relatively little research on the effect of the vaccine on oral HPV infection.[51] Herrero and colleagues[64] randomly assigned 7466 Costa Rican women to receive either the 2-valent HPV vaccine or hepatitis A control vaccine to evaluate the impact on cervical HPV 16 and 18 infection and precancerous lesions. The investigators estimated that the oral vaccine efficacy was 93.3% (one infection in the vaccine group vs 15 in the control group), based on oral specimens obtained 4 years after vaccination, but baseline oral HPV prevalence was unavailable for comparison. At the present time, prevention of oropharyngeal cancer is not a recognized indication for HPV vaccination.[65] There is no US Food and Drug Administration-approved diagnostic test for oral or oropharyngeal HPV infection.[63]


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