Elsevier

Oral Oncology

Volume 49, Issue 1, January 2013, Pages 1-8
Oral Oncology

Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas

https://doi.org/10.1016/j.oraloncology.2012.07.002Get rights and content
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open access

Summary

Background

Human papillomavirus (HPV) is a cause of oropharyngeal cancer, but a role for HPV in the etiology of oral cavity squamous cell carcinomas (OCSCC) remains uncertain.

Methods

We sought to estimate the etiologic fraction for HPV among consecutive, incident OCSCC diagnosed from 2005 to 2011 at four North American hospitals. DNA and RNA purified from paraffin-embedded tumors were considered evaluable if positive for DNA and mRNA control genes by quantitative PCR. Fifteen high-risk (HR) HPV types were detected in tumors by consensus PCR followed by type-specific HR-HPV E6/7 oncogene expression by quantitative reverse-transcriptase PCR. P16 expression was evaluated by immunohistochemistry (IHC). A study of 400 cases allowed for precision to estimate an etiologic fraction of as low as 0% (97.5% confidence interval, 0–0.92%).

Results

Of 409 evaluable OCSCC, 24 (5.9%, 95%CI 3.6–8.2) were HR-HPV E6/7 expression positive; 3.7% (95%CI 1.8–5.5) for HPV16 and 2.2% (95%CI 0.8–3.6) for other HR-HPV types. HPV-positive tumors arose from throughout the oral cavity (floor of mouth [n = 9], anterior tongue [6], alveolar process [4], hard palate [3], gingiva [1] and lip [1]) and were significantly associated with male gender, small tumor stage, poor tumor differentiation, and basaloid histopathology. P16 IHC had very good-to-excellent sensitivity (79.2%, 95%CI 57.9–92.9), specificity (93.0%, 95%CI 90.0–95.3), and negative-predictive value (98.6%, 95%CI 96.8–99.6), but poor positive-predictive value (41.3%, 95%CI 27.0–56.8) for HR-HPV E6/7 expression in OCSCC.

Conclusion

The etiologic fraction for HR-HPV in OCSCC was 5.9%. p16 IHC had poor positive predictive value for detection of HPV in these cancers.

Keywords

Oral cavity cancer
Human papillomavirus
p16 Immunohistochemistry
In situ hybridization
Predictive value

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