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

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

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 t...

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Published in:	Oral oncology 2013-01, Vol.49 (1), p.1-8
Main Authors:	Lingen, Mark W, Xiao, Weihong, Schmitt, Alessandra, Jiang, Bo, Pickard, Robert, Kreinbrink, Paul, Perez-Ordonez, Bayardo, Jordan, Richard C, Gillison, Maura L
Format:	Article
Language:	eng
Subjects:	Alphapapillomavirus - genetics Alphapapillomavirus - isolation & purification Alveoli Biological and medical sciences Carcinoma, Squamous Cell - virology Differentiation Etiology Female Gingiva Hematology, Oncology and Palliative Medicine Hospitals Human papillomavirus Human papillomavirus 16 Human papillomavirus 16 - genetics Human papillomavirus 16 - isolation & purification Humans Immunohistochemistry In situ hybridization Lip Male Medical sciences Middle Aged Mouth Mouth Floor - virology Mouth Neoplasms - virology mRNA Neoplasm Grading Neoplasm Staging Oncogene Proteins, Viral - analysis Oncogenes Oral cavity Oral cavity cancer oropharyngeal cancer Otolaryngology Otorhinolaryngology. Stomatology p16 Immunohistochemistry Palate Papillomavirus E7 Proteins - analysis Papillomavirus Infections - virology Polymerase chain reaction Predictive value Predictive Value of Tests Protein-Tyrosine Kinases - analysis Repressor Proteins - analysis Retrospective Studies Risk Factors Risk groups Sensitivity and Specificity Sex Factors squamous cell carcinoma Tongue Tongue Neoplasms - virology Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
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Summary:	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.
ISSN:	1368-8375 1879-0593