High-risk human papillomavirus (HR-HPV) is an etiologic factor in approximately 6% of cases of oral cavity squamous cell carcinoma (OCSCC), according to epidemiologic research.
The findings suggest that HPV-positive oropharyngeal SCC (OPSCC) constitutes "a unique epidemiologic and clinical entity" that is potentially preventable through vaccination, say Maura Gillison (The Ohio State University Comprehensive Cancer Center, Columbus, USA) and co-authors in Oral Oncology.
Gillison et al aimed to confirm and quantify an etiologic role for HPV in OCSCC. Their dataset was a large series of consecutive patients diagnosed with OCSCC at four North American hospitals between 2005 and 2011.
Of 409 tumors evaluated using quantitative polymerase chain reaction, 24 (5.9%) were positive for HR-HPV E6/E7 oncogene expression. HPV16 was the most common high-risk viral subtype, present in 3.7% of the sample, while six other high-risk subtypes in total accounted for 2.2% of the 409 tumors.
HPV-positive tumors were seen throughout the oral cavity, with the most common sites being the floor of mouth (n=9), anterior tongue (n=6), alveolar process (n=4), and hard palate (n=3). The anatomic distribution did not differ from that of HPV-negative tumors.
Interestingly, HPV-positive tumors were more likely than HPV-negative cases to be diagnosed in men, to be of early tumor stage, to be poorly differentiated, and to have basaloid histopathology.
When tumors were evaluated for p16 expression, 11.2% were positive by the H-score criteria, including 19 of 24 HR-HPV E6/7-positive tumors and 27 of 385 negative tumors. Thus, the sensitivity of p16 for HR-HPV E6/7 expression was 79.2%, specificity was 93.0%, positive predictive value was 41.3%, and negative predictive value was 98.6%.
Finally, when evaluated for the presence of additional HPV types, no HPV DNA sequences were detected in the 27 p16-positive/HPV-negative cases.
Gillison et al note that this is the largest and most comprehensive study of the issue to date, and that the HPV type distribution observed in the OCSCC tumors was much more diverse than for a corresponding series of oropharyngeal cancers reviewed by them in a previous study. "Studies that focus exclusively on HPV16 may therefore underestimate associations" between OCSCC and high-risk oral HPV infections in general, they say.
"Risk factor profiles and prognosis are different for HPV-positive and HPV-negative OPSCC," they remark, adding that investigation of HPV status, p16 status, and survival outcomes for OCSCC will be of interest for future research.
They conclude: "Our data may have important implications for the primary prevention of oral cavity carcinoma. If as high as 5% of the 263,000 annual cases of OCSCC are also due to HPV infection, a total of 35,650 oral cancer cases worldwide might be preventable through HPV vaccination."
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