Affiliation:
1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
2. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
4. Department of Epidemiology & Public Health, Albert Einstein College of Medicine, Bronx, NY, USA
5. University of California, Los Angeles School of Nursing, Los Angeles, CA, USA
6. DDL Diagnostic Laboratory, Rijswijk, the Netherlands
7. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Abstract
Abstract
Background
Human papillomavirus–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 semiannually using 30-second oral rinse and gargle specimens over 7 years. Initially, 447 participants were followed for 4 years as part of the Persistent Oral Papillomavirus Study, and a subset of 128 who showed persistent infections at the last Persistent Oral Papillomavirus Study visit had an additional visit, as part of the Men and Women Understanding Throat HPV Study, on average 2.5 years later. Extracted DNA from oral rinse and gargle specimens was amplified using polymerase chain reaction 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 a median time to clearance of 1.4 years (interquartile range = 0.5-3.9 years). After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV-16 viral load was statistically significantly associated with clearance (per 10-fold decrease in copy number: adjusted hazard ratio [aHR] = 2.51, 95% confidence interval [CI] = 1.20 to 5.26; P = .01). Adjusted analyses showed that oncogenic oral HPV clearance was lower among prevalent than incident-detected infections (aHR = 0.44, 95% CI = 0.35 to 0.55), among men than women (aHR = 0.74, 95% CI = 0.60 to 0.91), for older participants (aHR per 10 years increasing age = 0.81, 95% CI = 0.74 to 0.89), and among people living with HIV (aHR = 0.76, 95% CI = 0.60 to 0.95). One participant who had oral HPV-16 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 HPV-16 infections to date.
Funder
NIDCR, NIH
Multicenter AIDS Cohort Study (MACS) and Womens Interagency HIV Study (WIHS), now the MACS/WIHS Combined Cohort Study
National Institutes of Health
Baltimore CRS
Bronx CRS
Brooklyn CRS
Data Analysis and Coordination Center
Chicago-Cook County CRS
Chicago-Northwestern CRS
Connie Wofsy Women’s HIV Study, Northern California CRS
Los Angeles CRS
Metropolitan Washington CRS
Miami CRS
Pittsburgh CRS
UAB-MS CRS
UNC CRS
National Heart, Lung, and Blood Institute
Eunice Kennedy Shriver National Institute Of Child Health & Human Development
National Human Genome Research Institute
National Institute On Aging
National Institute Of Dental & Craniofacial Research
National Institute Of Allergy And Infectious Diseases
National Institute Of Neurological Disorders And Stroke
National Institute Of Mental Health
National Institute On Drug Abuse
National Institute Of Nursing Research
National Cancer Institute
National Institute on Alcohol Abuse and Alcoholism
National Institute on Deafness and Other Communication Disorders
National Institute of Diabetes and Digestive and Kidney Diseases
UCSF CTSA
Atlanta CFAR
UNC CFAR
UAB CFAR
Publisher
Oxford University Press (OUP)