Human papillomavirus negative high grade cervical lesions and cancers: Suggested guidance for HPV testing quality assurance.

BACKGROUND

Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL).

METHODS

There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process.

RESULT

Standard PCR testing detected HPV in 55.2 % (64/116) of initially "HPV-negative" samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented.

CONCLUSION

Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of "HPV negative" HSIL+ samples.

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K Cuschieri's institution has received research funding or gratis consumables to support research from the following commercial entities in the last 3 years: Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Abbott, Hologic and Vaccitech. M.P.’s institution received research funding, free-of-charge reagents, and consumables to support research in the last 3 years from Qiagen, Seegene, Abbott, and Roche, all paid to his employer. Sciensano the employer of M.A. received funding in the framework of Valgent and VALHUDES, which are 2 researcher induced protocols for evaluation of HPV tests on cervical and vaginal samples respectively (see Arbyn et J Clin Virol 2016 & 2018). M.A, did not receive any financial or material benefit from these projects.