Characterization of human papillomavirus (HPV) 16 E6 seropositive individuals without HPV-associated malignancies after 10 years of follow-up in the UK Biobank

Brenner, Nicole; Mentzer, Alexander J.; Hill, Michael; Almond, Rachael; Allen, Naomi E.; Pawlita, Michael; Waterboer, Tim

doi:10.1016/j.ebiom.2020.103123

Cited by 27 publications

(47 citation statements)

References 73 publications

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“…Second, the similarity in E6 seroprevalence by age (40–69 years) reported by Brenner et al. [4] . Presumably, most oral HPV infections that lead to E6 conversion are acquired prior to age 40, and thus E6 seroprevalence remains stable at older ages.…”

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confidence: 73%

“…Collectively, the observations of Brenner et al. [4] and the existing literature suggest that HPV16 E6 seropositivity is low in the general population, indicates oral/oropharyngeal HPV exposures (and that such exposures occur prior to age 40 years), marks high relative risk but low absolute risk of future oropharyngeal cancer, and is unlikely to represent a biomarker of prevalent disease. However, a few unexplained observations by Brenner et al.…”

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confidence: 98%

“…Brenner et al. [4] report higher E6 seropositivity in individuals with a higher number of lifetime sex partners, same-gender sex partners, early sexual debut, and in those seropositive for other sexually transmitted infections. These associations imply E6 seropositivity is a marker of exposure, consistent with acquisition of HPV infections at multiple anatomic sites, primarily through sexual activity [5] .…”

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confidence: 99%

“…In the December issue of EBioMedicine , Brenner et al. [4] report on the first large population-based study of HPV16 E6 seroepidemiology within the UK Biobank (ages 40–69 years). The key results include: 1) low prevalence of HPV16 E6 seropositivity (~0.8%); 2) seropositivity was associated with several markers of high-risk sexual behaviours; and 3) seropositivity was not associated with age, gender, or smoking status.…”

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confidence: 99%

“…Herein, we place the results of Brenner et al. [4] within the context of the field with respect to the biological/epidemiological meaning of HPV16 E6 seropositivity and the clinical implications for screening.…”

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confidence: 99%

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HPV16 E6 seropositivity and oropharyngeal cancer: Marker of exposure, risk, or disease?

Landy

Chaturvedi

2021

EBioMedicine

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confidence: 73%

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confidence: 98%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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HPV16 E6 seropositivity and oropharyngeal cancer: Marker of exposure, risk, or disease?

Landy

Chaturvedi

2021

EBioMedicine

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Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study

D’Souza

Tewari

Troy

et al. 2023

Cancer

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Background Human papillomavirus (HPV)‐related oropharyngeal cancer screening is being explored in research studies, but strategies to identify an appropriate population are not established. The authors evaluated whether a screening population could be enriched for participants with oncogenic HPV biomarkers using risk factors for oral HPV. Methods Participants were enrolled at Johns Hopkins Hospitals and Mount Sinai Icahn School of Medicine. Eligible participants were either men aged 30 years or older who had two or more lifetime oral sex partners and a personal history of anogenital dysplasia/cancer or partners of patients who had HPV‐related cancer. Oral rinse and serum samples were tested for oncogenic HPV DNA, RNA, and E6 or E7 antibodies, respectively. Participants with any biomarker were considered at‐risk. Results Of 1108 individuals, 7.3% had any oncogenic oral HPV DNA, and 22.9% had serum antibodies for oncogenic HPV E6 or E7. Seventeen participants (1.5%) had both oral and blood biomarkers. HPV type 16 (HPV16) biomarkers were rarer, detected in 3.7% of participants, including 20 with oral HPV16 DNA and 22 with HPV16 E6 serum antibodies (n = 1 had both). In adjusted analysis, living with HIV (adjusted odds ratio, 2.65; 95% CI, 1.60–4.40) and older age (66–86 vs. 24–45 years; adjusted odds ratio, 1.70; 95% CI, 1.07–2.70) were significant predictors of being at risk. Compared with the general population, the prevalence of oral HPV16 (1.8% vs. 0.9%), any oncogenic oral HPV DNA (7.3% vs. 3.5%), and HPV16 E6 antibodies (2.2% vs. 0.3%) was significantly elevated. Conclusions Enrichment by the eligibility criteria successfully identified a population with higher biomarker prevalence, including HPV16 biomarkers, that may be considered for screening trials. Most in this group are still expected to have a low risk of oropharyngeal cancer.

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A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Budhathoki

Diergaarde

Liu

et al. 2023

Intl Journal of Cancer

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Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold‐out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92‐0.95 in men and AUC = 0.92, 95% CI = 0.88‐0.95 in women). The 5‐year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

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Characterization of human papillomavirus (HPV) 16 E6 seropositive individuals without HPV-associated malignancies after 10 years of follow-up in the UK Biobank

Cited by 27 publications

References 73 publications

HPV16 E6 seropositivity and oropharyngeal cancer: Marker of exposure, risk, or disease?

HPV16 E6 seropositivity and oropharyngeal cancer: Marker of exposure, risk, or disease?

Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

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