Human Papillomavirus Genotype Detection in Oral Gargle Samples Among Men With Newly Diagnosed Oropharyngeal Squamous Cell Carcinoma

Abstract

IMPORTANCE The most common cause of oropharyngeal squamous cell carcinoma is human papillomavirus (HPV) infection, and currently the standard of care to determine the HPV infection status in this type of carcinoma is to use p16 immunohistochemistry as a surrogate marker of high-risk HPV infection. Although p16 immunohistochemistry is limited by the inability to determine the specific HPV genotypes, oral gargle samples may be a readily available source of HPV DNA for genotyping.OBJECTIVE To determine the specific HPV genotypes present in both oral gargle samples and tumor specimens. DESIGN, SETTING, AND PARTICIPANTSThis prospective, biomarker cohort study conducted at a single specialized cancer hospital in Florida screened approximately 800 potentially eligible participants from May 2014 through October 2017. To be eligible for participation, patients had to meet all of the following criteria: 18 years of age or older, male sex, newly diagnosed as having stage I to IV cancer of the oropharynx, a squamous cell carcinoma diagnosis, treatment naive or at least 4 weeks after chemoradiation or surgical treatment of other diseases, fully understand the study procedures and risks involved, and voluntarily agree to participate by signing an informed consent statement. MAIN OUTCOMES AND MEASURES Detection rate of HPV infection and HPV genotypes in oral gargle samples and tumor specimens.RESULTS A cohort of 204 male participants with newly diagnosed oropharyngeal squamous cell carcinoma was assessed in this prospective collection of comprehensive clinical data and oral gargle samples. Most study participants (190 [93.1%]) were white and ever smokers (114, 55.9%), with a median age of 61 years (range, 35-87 years). The HPV infection status could be assessed in 203 of 204 participants (99.5%) using oral gargle samples: 35 samples (17.2%) were negative for HPV infection, whereas 168 samples (82.8%) were positive for HPV infection. The detection rate of HPV genotypes was 93.0% in tumor specimens (160 specimens) and 82.8% (168 samples) in oral gargle samples. The oral gargle samples frequently had low-risk HPV genotypes that were not detected in tumors, but these low-risk genotypes were always a coinfection with high-risk genotypes. CONCLUSIONS AND RELEVANCEOral gargle samples can be used to detect the majority of clinically relevant HPV genotypes found in oropharyngeal squamous cell carcinoma, but the interpretation of HPV detected in these samples should be assessed with caution for general cancer risk assessment given that sensitive assays can concomitantly detect low-risk genotypes.

Evaluating the Utility and Prevalence of HPV Biomarkers in Oral Rinses and Serology for HPV-related Oropharyngeal Cancer

“…Utility of oncogenic HPV DNA detected by DEIA was evaluated in a recent systematic review (by our group) in 7 studies of OPSCC (n ¼ 5) or HNSCC (n ¼ 2) patients; our findings are consistent with the estimates in these heterogeneous studies, which found sensitivity of 55% and specificity of 94% for HPV-OPC (15). Some recent studies of incident HPV-OPC have reported high prevalence of oral oncHPV among cases, suggesting higher sensitivity than that found here (35). Performance of HPV16 E6 antibodies for HPV-OPC has been explored in a few studies previously, which reported high sensitivity (90%-96%) and specificity (96%-98%), comparable to that reported here (16,36,37).…”

Prevalence of Human Papillomavirus (HPV) DNA among Men with Oropharyngeal and Anogenital Cancers: A Systematic Review and Meta-Analysis

“…cancers was 45% (95% CI 26%-63%) as in Figure 3. Along with oncogenic HPV types, non-oncogenic types were detected in only two studies included for metaanalysis (Martin-Gomez et al, 2019;Strome et al, 2002).…”

“…One recent study from France was not included for the quantitative synthesis as the HPV DNA was detected by in situ hybridisation (ISH) which was much less sensitive than Polymerase Chain Reaction (PCR) (Mirghani et al, 2019). The association of HPV DNA in tissue samples from male oropharyngeal cases varied between 7.4%-93.0% (Bhosale et al, 2016;Martin-Gomez et al, 2019). There was a vast discrepancy regarding the period during which samples were collected and the number of samples tested.…”

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males

“…HPV types in the 9‐valent vaccine (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58) were assessed for sequential, type‐specific genital to oral infections because these types represent nearly all HPV types detected at the oral/pharynx 14 . Subjects with a genital and oral HPV DNA sample were included in this analysis (Figure 1).…”