HPV-Positive Oral Squamous Cell Carcinoma Is More Common in the Oropharynx of Young Male Non-Smokers
Terry Morgan, Jessica Hebert, Amy Schilling, Neil Gross, Josh Schindler, Chris Corless, Jody Hooper. OHSU, Portland; OSHU, Portland
Background: Recent data suggest that the prevalence of HPV-positive oropharyngeal cancers is increasing. If current trends continue, the annual number of HPV-positive oral cancers is expected to surpass the incidence of cervical cancer by 2020. The literature is mixed regarding the impact of tumor site and gender on the frequency of HPV-positive cancer. Methods of detection also vary; many pathologists use p16 immunostaining as a surrogate marker for HPV driven oral cancer, which may not be as predictive in the mouth as in the cervix. We compared the frequency of HPV-positive oral cancer at various biopsy sites and between patient genders. We also tested the predictive power of p16 compared with PCR and commonly employed high risk HPV tests.
Design: Retrospective analysis of 118 oral cancer biopsies collected at OHSU from 2004-2010 was performed. Biopsy site, patient age, gender, and smoking history were available for 87 cases. All H&E biopsies were reviewed to confirm diagnoses and all p16 (mtm/Roche) immunostained sections were scored as either positive or negative by two independent surgical pathologists. DNA was extracted from tumor blocks to obtain complete HPV genotype by PCR analysis (Diatherix), and high risk HPV screening by hybrid capture (Qiagen hc2) and Cervista (Hologic). A HPV result was considered positive if at least two HPV tests agreed. Results were analyzed by Chi-square analysis and ANOVA with post hoc testing.
Results: HPV-positive oral cancers were most common in the tonsil and base of tongue (oropharynx) biopsies (p<0.0001) of younger male (55 years vs 65 years) (p=0.0002) non-smokers (p=0.006). HPV was less common in oral cancer in females (6/23, 26%) compared with males (30/64, 47%). P16 staining had excellent negative predictive value (94 [83-98]) and good positive predictive value (87 [71-95]) compared to HPV DNA results. Most positive cases were HPV16 (27/33). PCR yielded two false negatives compared to hc2 and Cervista, perhaps due to paraffin extraction.
|HPV+ by PCR||HPV+ by hc2||P16 positive|
|Floor of Mouth (n=10)||0%||0%||10%|
|Roof of Mouth (n=6)||17%||17%||0%|