Long-term Persistence of Oral HPV Over 7 Years of Follow-up

Abstract

Background HPV-related oropharyngeal cancer (HPV-OPC) incidence is increasing but the natural history of the precursor, oral HPV, has not been well described. Methods This observational cohort study of people living with HIV and at-risk HIV uninfected people evaluated participants semi-annually using 30-second oral rinse/gargle specimens over 7 years. Initially, 447 subjects were followed for four years as part of the POPS Study, and a subset of 128 showing persistent infections at the last POPS visit had an additional visit, as part of MOUTH Study, on average 2.5 years later. Extracted DNA from oral rinse/gargle specimens were amplified using PCR and type-specification of 13 oncogenic HPV types. Risk factors for oncogenic oral HPV clearance were evaluated using Cox models. Results The majority of oncogenic oral HPV infections cleared quickly with median time to clearance of 1.4 years [IQR=0.5-3.9]. After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV16 viral load was statistically significantly associated with clearance (Per 10-fold decrease in copy number: adjusted hazard ratio [HR]=2.51, 95% confidence interval [CI]=1.20-5.26, p=.01) Adjusted analyses showed oncogenic oral HPV clearance was lower among prevalent than incident detected infections (aHR=0.44, 95%CI=0.35-0.55), among men than women (aHR=0.74, 95%CI=0.60-0.91), for older participants (aHR per 10 years increasing age=0.81, 95%CI=0.74-0.89), and among people living with HIV (aHR=0.76, 95% CI = 0.60-0.95). One participant who had oral HPV16 consistently detected at 10 study visits over 4.5 years was subsequently diagnosed with HPV-OPC. Conclusions This prospective study of oncogenic oral HPV infection is the longest and largest quantification of oral HPV16 infections to date.

Salivary High-Risk Human Papillomavirus (HPV) DNA as a Biomarker for HPV-Driven Head and Neck Cancers

“…Salivary HR-HPV positivity at the very early stages of HNC has also been proven in two recent studies in which longitudinal salivary HPV testing was coupled with clinical investigations to detect HNC in asymptomatic individuals. 13,14 These studies, together with the present findings, highlight the possible utility of screening programs based on longitudinal salivary HR-HPV DNA testing for the early detection of HPV-HNC. Furthermore, the present findings indicate the potential of salivary HR-HPV DNA testing for HNC patient monitoring.…”

“…This hypothesis is attested to in two recent studies in which it was confirmed that longitudinal salivary HR-HPV testing, coupled with clinical investigations, identified HPV-HNC in asymptomatic individuals. 13,14 However, varying degrees of sensitivity of salivary HPV detection in HPV-HNC patients have been reported. 15e20 A general consensus, therefore, has not been reached regarding the utility of HPV detection for HPV-HNC identification and monitoring.…”

Determinants of dentists’ readiness to assess HPV risk and recommend immunization: A transtheoretical model of change-based cross-sectional study of Ontario dentists

“…HPV infections may remain asymptomatic or may be detected as wart-like oral lesions, with most HPV oral infections tend to clear within 18 months [ 8 ]. However, a small percentage of HPV oral infections may persist for a longer period of time and transform into malignant lesion, particularly the high risk of HPV oral infections that are linked to HPV types 16 and 18 [ 9 ].…”

Determining the utility of a screening program to reduce the incidence of HPV driven oropharyngeal cancer

“…After surgical excision of the clinically occult 2 mm tonsillar HPV-OPC, HPV DNA became undetectable in saliva. A further report of persistent oral HPV 16 infection with incident diagnosis of HPV-OPC also demonstrated a rise in oral HPV 16 from low to high intensity, prior to the diagnosis of an invasive malignancy [ 5 ].…”