A Longitudinal Study of Human Papillomavirus 16 L1, E6, and E7 Seropositivity and Oral Human Papillomavirus 16 Infection

Abstract

Background Individuals with HPV infections can develop IgG antibodies to HPV proteins including the L1 capsid and E6 and E7 oncoproteins. Evidence on whether L1 antibodies reduce the risk of cervical HPV infection is mixed, but this has not been explored for oral HPV infections. Antibodies to HPV16’s E6 oncoprotein have been detected in some oropharyngeal cancer cases years prior to cancer diagnosis, but it is unknown if these antibodies are associated with oral HPV16 DNA. Methods Enzyme linked immunosorbent assays tested for serum antibodies to HPV16’s L1 capsid in 463 HIV-infected and 293 HIV-uninfected adults, and for antibodies to recombinantly expressed E6 and E7 oncoproteins to HPV16 in 195 HIV-infected and 69 HIV-uninfected cancer-free participants at baseline. Oral rinse samples were collected semi-annually for up to three years and tested for HPV DNA using PGMY 09/11 primers. Adjusted Poisson, logistic, and Wei-Lin-Weissfeld regression models were utilized. Results HPV16 L1 seroreactivity did not reduce the subsequent risk of incident oral HPV16 infection in unadjusted (HR=1.4, 95%CI=0.59–3.3) or adjusted (aHR=1.1, 95%CI=0.41–3.0) analysis. Antibodies to HPV16 E6 and E7 oncoproteins were detected in 7.6% and 3.4% of participants respectively, but they were not associated with baseline oral HPV16 DNA prevalence or oral HPV16 persistence (each p-value>0.40). Conclusions Naturally acquired HPV16 L1 antibodies did not reduce the risk of subsequent oral HPV16 infection. HPV16 E6 and E7 seropositivity was not a marker for oral HPV16 infection in this population without HPV-related cancer.

Genetic polymorphisms and HPV infection in oral squamous cell carcinomas

“…While the prevalence of detecting HPV in OSCC was 46.5% in a total of 4680 samples from 94 studies [12], we found that among MD Anderson head and neck cancer cases, HPV16 was detected in approximately 25% of the tumors in the oral cavity, and 80% in oropharynx [15]. For HPV-positive tumors, HPV16 has been identified in 90-95% of the tumors followed by HPV31, 33 and 18 [16 ]. It has been suggested that certain subgroups of OSCC patients are more likely to be HPV16-positive due to effect of potential genetic variants on HPV infection rates.…”

“…In addition, other studies also have demonstrated that HPV infection, particularly HPV16, was associated with an increased risk of OSCC, independent of exposure to alcohol and tobacco [20,24]. In a multi-institutional international study of 1670 cases and 1732 controls, Herrero and colleagues found that HPV16 L1, E6, and E7 seropositivity was a significant risk for OSCC [16 ]. In our matched pair analysis at our institution, we found 40.8% of 120 patients with squamous carcinoma of the head and neck to be HPV-16 seropositive but only 9.2% of matched cancer-free controls (adjusted OR = 6.7, 95% CI = 3.0-14.9) [17].…”

Deregulation of SYCP2 predicts early stage human papillomavirus‐positive oropharyngeal carcinoma: A prospective whole transcriptome analysis

“…Of course, high‐risk HPV infection can be a transient phenomenon and detection alone may not be sufficient to provide a causal association. Many studies have previously shown the presence of HPV subtypes even in normal oral cavity tissue . Gillison et al .…”

HPV-Associated Head and Neck Cancer: Unique Features of Epidemiology and Clinical Management

“…The prevalence of HPV 16 in oral rinse samples from healthy adults ranges from 1.0% to 7.6% (21, 22). Only a fraction of those with oral HPV infection will develop HPV-positive OPC after many years.…”