Most oropharyngeal
squamous cell carcinomas (SCC) and histologic variants harbor transcriptionally active human papillomavirus (HPV). While HPV
DNA can be found in many non-oropharyngeal head and neck
carcinomas, transcriptionally active HPV is rare.
Verrucous carcinoma is a variant with bland cytology, warty appearance, locally destructive growth, and lack of
metastasis when lacking a frankly invasive
carcinoma component. Studies have shown variable rates of HPV
DNA and p16
protein expression in such
tumors but still have not clearly addressed if the virus has
biological activity or clinical relevance in the positive cases. Department files were searched for verrucous
neoplasms, including pure
verrucous carcinoma,
verrucous carcinoma with dysplasia or minimal invasion, and SCC arising in
verrucous carcinoma (ie, having a major component of frankly invasive
carcinoma). p16 immunohistochemistry, HPV
DNA polymerase chain reaction (PCR) and E6/E7
mRNA reverse transcription PCR for high-risk HPV types were performed. Of the 49 cases, 6 (12.2%) showed strong (>50%) staining for p16. HPV
DNA was detected in 7/49 (14.3%) cases, but only one case was positive for both p16, and HPV
DNA. A total of 36 cases yielded sufficient
RNA for RT-PCR (18
verrucous carcinomas, 13 atypical
verrucous carcinomas, and 5 SCC arising in
verrucous carcinoma). All 36 were negative, including the four p16-positive and three HPV
DNA-positive
tumors tested. Although a minority of
verrucous carcinoma lesions are p16 and HPV
DNA positive, transcriptionally active high-risk HPV is uniformly absent. These findings argue that
verrucous carcinoma and its related
squamous cell carcinomas are not HPV-driven
tumors.