Antibodies against HPV16 early proteins have been shown to be promising biomarkers for the identification of HPV-driven oropharyngeal cancer (HPV-OPC) among OPC cases in multiple studies. A systematic literature search was performed to identify original research articles comparing HPV early antigen serology with established reference methods to determine molecular HPV tumor status. Random-effects models were used to calculate summary estimates for sensitivity and specificity of HPV16 E2, E6 and E7 serology for HPV-OPC. Subgroup analyses were performed to explore heterogeneity across studies and describe variables associated with test performance. We identified n = 23 studies meeting all eligibility criteria and included these in the meta-analysis. E6 serology showed the best performance with pooled sensitivity and specificity estimates of 83.1% (95% confidence interval (CI) 72.5–90.2%) and 94.6% (95% CI 89.0–97.4%), respectively, while E2 and E7 serological assays were highly specific (E2: 92.5% (95% CI 79.1–97.6%); E7: 88.5% (95% CI 77.9–94.4%)) but moderately sensitive (E2: 67.8% (95% CI 58.9–75.6%); E7: 67.0% (95% CI 63.2–70.6%)). Subgroup analyses revealed increased pooled sensitivity for bacterially (89.9% (95% CI 84.5–93.6%)) vs. in vitro expressed E6 antigen (55.3% (95% CI 41.0–68.7%)), while both showed high specificity (95.2% (95% CI 93.0–96.7%) and 91.1% (95% CI 46.6–99.2%), respectively). Pooled specificity estimates for HPV16 E2, E6 and E7 serology were significantly lower in studies utilizing HPV DNA PCR as the only molecular reference method compared to those using a combination of any two reference methods (HPV DNA, RNA, in situ hybridization (ISH), p16 immunohistochemistry (IHC)), or histopathological reference methods (ISH or p16 IHC) as stand-alone marker. In conclusion, HPV16 E6 seropositivity is a highly sensitive and specific biomarker for HPV-OPC. However, its performance differs between serological assays and depends on molecular reference methods.

INTRODUCTION: Individuals with a family history (FH) of colorectal cancer (CRC) are at increased risk of CRC. We aimed to assess the objective role and subjective perception of risk factors of colorectal neoplasia within this high-risk group. METHODS: Questionnaire and screening colonoscopy results were obtained from individuals aged 40–54 years with a reported FH of CRC in a first-degree relative in a multicenter cross-sectional study in Germany. Descriptive statistics characterized the cohort and distribution of risk factors. Multivariable logistic regression was used to derive adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) to evaluate factors associated with colorectal neoplasia and with subjectively perceived increased CRC-risk. RESULTS: Among 922 participants, 220 (23.9%) were diagnosed with colorectal neoplasia, 63 (6.8%) of these being advanced lesions. Strong associations with advanced neoplasia were observed for obesity (aOR 2.44, 95% CI 1.12–5.22), smoking (aOR 1.47, 95% CI 1.14–1.88 per 10-pack-years) and physical activity <45 minutes per day (aOR 2.51, 95% CI 1.11–5.25). For smoking and physical activity, but not for obesity, similar associations were also seen with any colorectal neoplasia. No associations were seen with number and age at diagnosis of affected family members. By contrast, the latter factors, but none of the behavioral factors were strongly associated with subjectively perceived CRC-risk. DISCUSSION: Within a cohort of individuals aged 40–54 years with a FH of CRC, obesity, smoking, and lack of physical activity represented the most prominent modifiable risk factors for the development of advanced colorectal neoplasia but did not significantly impact risk perception in these high-risk participants.