Feasibility and Accuracy of Menstrual Blood Testing for High-risk Human Papillomavirus Detection With Capture Sequencing

Jingjing Zhang,Zhen Zeng,Rui Tian,Chen Cao,Zifeng Cui,Ronghua Shang,Wenjia Liang,Qifen Gong,Zheng Hu,Xun Tian,Sisi Huang,Ye Chen

doi:10.1001/jamanetworkopen.2021.40644

Abstract

High-risk human papillomavirus (hrHPV) persistent infection is the major etiology of cervical precancer and cancer. Noninvasive self-sampling HPV testing is a promising alternative cervical cancer screening for avoiding stigma and improving patient willingness to participate. To investigate the feasibility and accuracy of menstrual blood (MB) hrHPV capture sequencing in hrHPV detection. This cohort study collected 137 sanitary pads from 120 women who were premenopausal and had hrHPV as detected by cervical HPV GenoArray testing. Patients were recruited from September 1, 2020, to April 1, 2021, at Central Hospital of Wuhan, China. Target capture sequencing was performed to determine hrHPV genotypes in MB. Sanger sequencing was performed as the criterion standard for detecting hrHPV genotypes among enrolled women. Data were analyzed from April 1 through June 1, 2021. Complete concordance, incomplete concordance, and discordance of MB hrHPV capture sequencing and conventional HPV testing were defined according to genotype overlapping levels. Concordance of the 2 detection methods and comparative power of MB hrHPV capture sequencing during different menstrual cycle days (MCDs) were the main outcomes. A total of 120 enrolled women with hrHPV (mean [SD; range] age, 33.9 [6.9; 20.0 -52.0] years) provided 137 sanitary pads. The overall concordance rate of MB hrHPV capture sequencing and cervical HPV testing was 92.7% (95% CI, 88.3%-97.1%), with a κ value of 0.763 (P < .001). Among 24 samples with incomplete concordance or discordant results, 11 samples with additional hrHPV genotypes (45.8%), 5 true-negative samples (20.8%), and the correct hrHPV genotypes of 2 samples (8.3%) were correctly identified by MB hrHPV capture sequencing. MB hrHPV detection of hrHPV was equivalent on different MCDs, with an MB hrHPV-positive rate of 27 of 28 patients (96.4%) for MCD 1, 52 of 57 patients (91.2%) for MCD 2, 27 of 28 patients for MCD 3, 4 of 4 patients (100%) for MCD 4, and 3 of 3 patients (100%) for MCD 5 (P = .76). The sensitivity of the MB hrHPV capture sequencing was 97.7% (95% CI, 95.0%-100%). These findings suggest that MB hrHPV capture sequencing is a feasible and accurate self-collected approach for cervical cancer screening. This study found that this method is associated with superior performance in identification of HPV genotypes and true-negative events compared with cervical HPV testing.

Highlights

Persistent infection of high-risk human papillomavirus is associated with various Human papillomavirus (HPV)-related precancers and cancers.[1]
This study found that this method is associated with superior performance in identification of HPV genotypes and truenegative events compared with cervical HPV testing
We defined the degree of detection concordance between menstrual blood (MB) high-risk human papillomavirus (hrHPV) capture sequencing and conventional HPV testing as follows: if there was at least 1 overlapping hrHPV genotype between testing methods among all genotypes found in 1 patient's sample, it was defined as concordance

Summary

Introduction

Persistent infection of high-risk human papillomavirus (hrHPV) is associated with various HPV-related precancers and cancers.[1] In recent years, HPV testing has gradually become the primary method for cervical cancer screening.[2] cervical cancer screening has been found to be helpful in decreasing the incidence and mortality rate of cervical cancer, various factors (including medical infrastructure, culture and mentality, and society) may influence women’s acceptance of clinician sampling.[3] Among women with overdue screening, 29% were afraid of the stigma and 14% were had fear of pain in 2 studies.[4,5] Self-sampling HPV testing is a proposed alternative cervical cancer screening for avoiding stigma and improving participation.[6] to our knowledge, most existing self-sampling HPV studies were based on various sampling brushes inserted into the vagina, and patients may experience discomfort during sampling.[7,8,9,10,11] Compared with these methods, menstrual blood (MB) collection is associated with less stigma and pain

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Discussion

Conclusion