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

Abstract

This cohort study compares high-risk human papillomavirus (HPV) detection using menstrual blood testing with capture sequencing vs cervical HPV testing.

Key Points

Question

Is menstrual blood high-risk human papillomavirus (hrHPV) capture sequencing a feasible and accurate approach for HPV detection?

Findings

In this cohort study of 120 women with hrHPV, menstrual blood hrHPV capture sequencing had a high concordance rate with cervical HPV testing and offered advantages in the detection of additional hrHPV genotypes and true negative samples.

Meaning

These findings suggest that menstrual blood hrHPV capture sequencing is a feasible and accurate self-collected approach for hrHPV detection.

Abstract

Importance

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.

Objective

To investigate the feasibility and accuracy of menstrual blood (MB) hrHPV capture sequencing in hrHPV detection.

Design, Setting, and Participants

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.

Main Outcomes and Measures

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.

Results

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%).

Conclusions and Relevance

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.