The Triage Effectiveness of an Extended High-Risk Human Papillomavirus Genotyping Assay for Women with Cytology Showing Atypical Squamous Cells of Undetermined Significance in China

Abstract

Purpose

Little is known about the performance of extended high-risk human papillomavirus (HR-HPV) genotyping triage of cytology showing atypical squamous cells of undetermined significance (ASC-US). This study aims to evaluate the effectiveness of triage with different HR-HPV genotype models among women with ASC-US.

Materials and Methods

In this study, all women who underwent cervical cytology and HR-HPV genotyping were enrolled from 2014 to 2017 in China, and those with cytology showing ASC-US were referred for colposcopy and/or biopsy. The endpoint was histological detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). The outcome indicators were the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs) and colposcopy referral rates.

Results

In all, 56,788 women were enrolled in this study, and 2658 (4.97%) women were reported to have ASC-US; 10.1% (242/2393) of women with ASC-US were identified as having CIN2+. The HR-HPV infection rate was 95.0% among all women with ASC-US who were identified as CIN2+, and the top five genotypes with prevalence and risk of CIN2+ were HPV16 (OR=26.38), HPV58 (OR=7.04), HPV18 (OR=4.44), HPV33 (OR=3.38), HPV31 (OR=2.97) and HPV52 (OR=2.96). The HPV16/18/31/33/52/58 model achieved higher sensitivity [91.3 (87.8–94.9)], specificity [70.0 (68.1–72.0)], PPV [25.5 (22.4–28.2)] and NPV [98.6 (97.3–98.7)] for the triage of ASC-US patients than the other HR-HPV-type combination models, but the colposcopy referral rate (36.2%) was significantly lower than that of the recommended HR-HPV nongenotyping model (47.6%).

Conclusion

This study confirms that the specific HR-HPV genotype HPV16/18/31/33/52/58 is an alternative strategy for ASC-US triage and can effectively reduce the high burden of colposcopy referrals in China.

Keywords:

• human papillomavirus
• genotyping
• atypical squamous cells of undetermined significance
• cervical intraepithelial neoplasia

Acknowledgments

The authors would like to thank the Fujian Province Cervical Lesions Screening Cohorts Investigators for planning and conducting the trial and for providing the biological specimens and data for the present study. Above all, we are grateful to the patients who made this study possible.

Abbreviations

HR-HPV, high-risk human papillomavirus; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; CIN, cervical epithelial neoplasia; TCT, liquid-based cytology; DNA, deoxyribonucleic acid; ECC, endocervical curettage; PPV, positive predictive value; NPV, negative predictive value; OR, odds ratio.

Ethics Approval

This study was conducted in accordance with the Declaration of Helsinki, and was approved by the Ethics Committees of the Fujian Maternity and Child Health Hospital (2014-045).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests for this work.

Additional information

Funding

This work was supported by grants from the Fujian Provincial Natural Science Foundation of China (grant no. 2017J01232) and the Fujian Maternity and Child Health Hospital Natural Science Foundation (grant no. YCXM18–18).