Dataset Information

Humoral Response to HPV16 Proteins in Persons with Anal High-Grade Squamous Intraepithelial Lesion or Anal Cancer.

ABSTRACT:

Background

This study was launched to evaluate the association of early and late antibodies to human papillomavirus 16 (HPV16) detection and risk of anal high-grade squamous intraepithelial lesions (HSIL) or cancer.

Methods

We analyzed data from persons with anal HSIL or cancer and controls from a case-control study in Seattle, Washington. Sera were evaluated for HPV16 early (E1, E2, E4, E6, and E7) and late (L1) antibodies by multiplex serology. Logistic regression models were used to assess serologic associations with risk of anal HSIL or cancer.

Results

The study included 67 participants with anal HSIL, 116 with anal cancer, and 830 population-based controls. HPV16 seropositivity to L1 [adjusted OR (aOR), 13.8; 95% confidence interval (CI), 7.4-25.8], E4 (aOR, 2.3; 95% CI, 1.1-4.5), and E6 (aOR, 4.9; 95% CI, 1.1-21.2) was associated with HSIL; and detection of all antibodies to HPV16 late and early proteins was associated with increased risk of anal cancer ranging from aOR 1.7 to 32.5 [L1 aOR, 12.5 (95% CI, 7.3-21.7); E1 aOR, 24.9 (95% CI, 10.3-59.9); E2 aOR, 6.3 (95% CI, 3.4-11.7); E4 aOR, 2.8 (95% CI, 1.6-4.8); E6 aOR, 32.5 (95% CI, 14.2-74.4); and E7 aOR, 1.7 (95% CI, 1.0-3.0)].

Conclusions

HPV serologic markers proved to be specific for identifying anal cancer. HPV16 E6 seropositivity is relatively uncommon in persons without anal cancer.

Impact

This large study comprehensively describes the distinct antibody responses to the HPV16 proteins in persons with anal HSIL or anal cancer. Antibodies to HPV16 E6 should be further evaluated as a potential biomarker for anal cancer prevention.

SUBMITTER: Stankiewicz Karita HC

PROVIDER: S-EPMC7642112 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveHIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV.DesignBetween 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies.MethodsParticipants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone.Results83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively.ConclusionAnal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.