The Prevalence, Anatomic Distribution and Significance of HPV Genotypes in Head and Neck Squamous Papillomas as Detected by Real-Time PCR and Sanger Sequencing

Squamous papillomas (SPs) of the head and neck are generally regarded as a human papillomavirus (HPV)-driven process, but reported rates of HPV detection vary dramatically. Moreover, they are generally considered a benign condition, but the detection of high risk HPV types is commonly reported. This latter finding is particularly disturbing to clinicians and their patients given the alarming rise of HPV-associated head and neck cancer. The capriciousness of HPV detection reflects in large part differences in methodologies. The purpose of this study was to review an institutional experience using a state of the art detection method to determine the presence, type and anatomic distribution of HPV in head and neck SPs. The surgical pathology files of the Mount Sinai Hospital were reviewed for all SPs that had undergone HPV testing between 2012 and 2018. HPV screening was performed on tissue blocks with real-time PCR using primers designed to target the L1 region of low and high-risk HPV types. Genotyping was performed on HPV positive cases. HPV detection was repeated for cases that were originally reported to be positive for high risk HPV. 134 cases had undergone HPV analysis. Of the 131 with sufficient cellular material, 2 were excluded because the HPV testing yielded inconclusive results. The remaining 129 cases were the basis of this study. Thirty-eight cases (29%) were HPV positive and 91 (71%) were negative. The most common genotype was HPV 6 (n = 27, 71%), followed by HPV 11 (n = 10, 26%). One case (1%) was HPV positive but the genotype could not be determined. Of the HPV negative cases, 3 were originally reported as HPV 16 positive but found to be HPV negative on re-review and repeat testing. SPs arising in the larynx were more likely to harbor HPV than those arising in the oral cavity and oropharynx (64% vs. 10%, p < 0.00001). Similarly, recurrent respiratory papillomatosis (RRP) were much more likely to be HPV positive than solitary SPs (71% vs. 10%, p < 0.00001). Almost a third of head and neck SPs harbor HPV, but incidence is highly dependent on anatomic site. Those arising in the larynx are more prone to be HPV-driven than those arising in the oral cavity and oropharynx, particularly when occurring in the setting of RRP. High risk HPV could not be confirmed in any of the cases. Routine HPV testing as a strategy to unmask potentially malignant lesions harboring high risk HPV is not likely to be useful.