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

ACCESS DATA

Similar Datasets

Project description:BackgroundThe incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.MethodsWe conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.ResultsOf 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).ConclusionsAmong participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

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.