1. Women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) who have high-grade human papillomavirus (HPV) 16/18 positivity are at a high risk for cervical cancer and referral for colposcopy is advised.
2. For other HPV types, local decision thresholds determined from pretest-posttest probability plots can help guide the decision to avoid colposcopy or to recommend repeated testing.
Evidence Rating Level: 1 (Excellent)
Study Rundown: For women with high-grade HPV lesions, referral for colposcopy and biopsy is usually recommended. ASC-US and LSIL are considered minor cervical abnormalities, and women with one of these conditions have only a moderately increased cervical cancer risk. Due to the strong correlation between infection with high-risk HPV (hrHPV) and cervical cancer, hrHPV testing has become the standard follow-up for ASC-US or LSIL. However, most samples will test positive, and the recommended colposcopy for all of these women has substantial burden and cost. Therefore, this study sought to evaluate the accuracy of genotyping for HPV types 16 and 18, which cause approximately 70% of the cases of cervical cancer. The researchers also assessed the use of genotyping as a second triage step to help guide referrals for colposcopy after hrHPV testing in women with ASC-US or LSIL. This systemic review and meta-analysis found that although there is poor sensitivity, testing for HPV types 16 and 18 may be useful as a triage step after hrHPV testing, with colposcopy referral advised for women with HPV 16/18 positivity. For other HPV types, local decision thresholds determined from pretest-posttest probability plots can help guide the decision to avoid colposcopy or recommend repeated testing.
A strength of this study is the high number of women (8587 with ASC-US and 5284 with LSIL) included in this meta-analysis of 24 select studies of moderate to good quality. Also, the researchers carried out a systematic review of genotyping for HPV 16/18 as a triage test, which had not been previously done. One of the limitations of this study is that there was heterogeneity among study methods and techniques. In addition, there was inadequate data to evaluate the accuracy of separate assays.
In-Depth [systematic review and meta-analysis]: This study analyzed 24 studies of moderate to good quality that included 8587 women with ASC-US and 5284 with LSIL. This study sought to assess the accuracy of genotyping for HPV types 16 and 18 in order to evaluate its use as a triage step after hrHPV testing. Test results for HPV 16/18 were considered positive if presence of HPV 16 or HPV 18 was found and negative in the absence of both types. Although genotyping was found to be more specific than hrHPV testing, there was a loss in sensitivity. For cervical intraepithelial neoplasia with a threshold grade of <2, the pooled specificity of HPV 16/18 genotyping was 83% (95% CI, 80% to 86%) and 76% (CI, 74% to 79%) for women with ASC-US and LSIL, respectively. HPV 16/18 genotyping for CIN3+ in women with either ASC-US or LSIL had a pooled sensitivity of approximately 70%. For CIN3+, the average risk for HPV 16/18-positive women was 17% for those with ASC-US and 19% for those with LSIL. For either ASC-US or LSIL, the average risk was 5% for women who were hrHPV-positive but HPV 16/18-negative. Women who have HPV 16/18 positivity are at a high risk for cervical cancer and referral for colposcopy was advised.
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