Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review

TY - JOUR

T1 - Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests

T2 - systematic review

AU - Rebolj, Matejka

AU - Bonde, Jesper

AU - Njor, Sisse Helle

AU - Lynge, Elsebeth

PY - 2011/5/28

Y1 - 2011/5/28

N2 - Objective: To 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). Design: Systematic review. Data: sources PubMed. Study selection: Randomised 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. Participants: Women in the baseline screening rounds of the trials. Interventions: Hybrid 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. Results: Owing 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/covaried 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. Conclusions: Although 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.

AB - Objective: To 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). Design: Systematic review. Data: sources PubMed. Study selection: Randomised 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. Participants: Women in the baseline screening rounds of the trials. Interventions: Hybrid 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. Results: Owing 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/covaried 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. Conclusions: Although 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.

KW - Adult

KW - Cervical Intraepithelial Neoplasia

KW - Early Detection of Cancer

KW - Female

KW - Humans

KW - Middle Aged

KW - Nucleic Acid Hybridization

KW - Papillomavirus Infections

KW - Randomized Controlled Trials as Topic

KW - Uterine Cervical Dysplasia

KW - Uterine Cervical Neoplasms

U2 - 10.1136/bmj.d2757

DO - 10.1136/bmj.d2757

M3 - Journal article

C2 - 21606136

SN - 0959-8146

VL - 342

SP - d2757

JO - BMJ

JF - BMJ

ER -