Dataset Information

Prospective comparison of hybrid capture 2 and SPF??-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China.

ABSTRACT:

Objective

To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers.

Methods

Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF??-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible human papillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed.

Results

The overall agreement between HC2 and SPF??-LiPA for detecting carcinogenic HPV was 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positive and LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%-27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%; 95% CI=8.57%-11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95% CI=2.44%-2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%-1.92%) women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was 8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54.

Conclusion

The noticeable high risk of CIN2+ in women infected with cross-reacted non-carcinogenic HPV and low risk in those with miss-to-detective carcinogenic HPV supported an overall good clinical performance of HC2 for a general cervical cancer screening.

SUBMITTER: Dong L

PROVIDER: S-EPMC5540725 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Prospective comparison of hybrid capture 2 and SPF₁₀-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China.

Dong Li L Feng Rui Mei RM Zhang Li L Xu Xiao Qian XQ Zhao Xue Lian XL Wang Margaret Zhuoer MZ Qiao You Lin YL Zhao Fang Hui FH

Journal of gynecologic oncology 20170605 5

<h4>Objective</h4>To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers.<h4>Methods</h4>Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF₁₀-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Ten-year cumulative incidence r ...[more]

PMID: 28657227

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Project description:Hybrid Capture 2 (hc2), a clinical test for carcinogenic human papillomavirus (HPV) DNA, has proven to be a sensitive but only modestly specific predictor of cervical precancer and cancer risk. Some of its nonspecificity for clinical end points can be ascribed to cross-reactivity with noncarcinogenic HPV genotypes. However, the reference genotyping tests that have been used for these comparisons are also imperfect. We therefore sought to describe further the HPV genotype specificity of hc2 by comparing the hc2 results to paired results from two related PGMY09/11 L1 primer-based HPV genotyping assays: Linear Array (LA) and its prototype predecessor, the line blot assay (LBA). LA and LBA results were considered separately and combined (detection by either assay or both assays) for 37 individual HPV genotypes and HPV risk group categories (carcinogenic HPV > noncarcinogenic HPV > negative). Baseline specimens from 3,179 of 3,488 (91.5%) women referred to ALTS (a clinical trial to evaluate the management strategies for women with atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions) because of an ASCUS Papanicolaou smear were tested by all three assays. Among single-genotype infections with genotypes targeted by hc2 as detected by either PCR assay, HPV genotype 35 (HPV35) (86.4%), HPV56 (84.2%), and HPV58 (76.9%) were the most likely to test positive by hc2. Among single-genotype infections with genotypes not targeted by hc2 as detected by either assay, HPV82 (80.0%), HPV66 (60.0%) (recently classified as carcinogenic), HPV70 (59.1%), and HPV67 (56.3%) were the most likely to test positive by hc2. Among women who tested negative for carcinogenic HPV by both PCR tests and were positive for noncarcinogenic HPV by either test, 28% of women were hc2 positive. Conversely, 7.8% of all hc2-positive results in this population were due to cross-reactivity of hc2 with untargeted, noncarcinogenic HPV genotypes. In conclusion, hc2 cross-reacts with certain untargeted, noncarcinogenic HPV genotypes that are phylogenetically related to the targeted genotypes, but the degree of cross-reactivity may be less than previously reported.

Project description:ObjectiveTo determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ≥ 1 relative light units/cut-off level (rlu/co).DesignSystematic review.Data sourcesPubMed.Study selectionRandomised controlled trials in primary cervical screening using hybrid capture 2 testing in the intervention arms. Articles published until August 2010 were included if the numbers of women with positive test results and with cervical intraepithelial neoplasia were stratified by hybrid capture 2 cut-off levels.ParticipantsWomen in the baseline screening rounds of the trials.InterventionsHybrid capture 2 screening in the baseline round including the diagnostic follow-up as practised in the randomised controlled trials and as reported by hybrid capture 2 cut-off values.ResultsOwing to heterogeneity in the trials, meta-analysis was not possible. Including cut-off values up to ≥ 10 rlu/co, 25 observation points were available for analysis. The relative sensitivity for cervical intraepithelial neoplasia grade III or higher at cut-off levels of ≥ 2, ≥ 4 or ≥ 5, and ≥ 10 rlu/co compared with a cut-off level of ≥ 1 rlu/co varied by trial, but at their lowest they were 0.97, 0.92, and 0.91, respectively. A similar pattern was observed for cervical intraepithelial neoplasia grade II or higher. The specificity would increase by at least 1%, 2%, and 3%, respectively, so that up to 24%, 39%, and 53%, of positive hybrid capture 2 test results not associated with high grade neoplasia could be avoided. Only two outliers existed to this general pattern.ConclusionsAlthough the data were derived from the baseline screening rounds only, the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥ 2 rlu/co and ≥ 10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening, which require 90% or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥ 1 rlu/co. The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening; this seems reasonably safe and is significantly less burdensome for women.