Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening?

Abstract

Several countries are in the process of switching to high-risk human papillomavirus (hrHPV) testing for cervical cancer screening. Given the multitude of available tests, validated assays which assure high-quality screening need to be identified. A systematic review was conducted to answer the question which hrHPV tests fulfil the criteria defined by an international expert team in 2009, based on reproducibility and relative sensitivity and specificity compared to Hybrid Capture-2 or GP5+/6+ PCR-enzyme immunoassay. These latter two hrHPV DNA assays were validated in large randomized trials and cohorts with a follow-up duration of 8 years or more. Eligible studies citing the 2009 guideline were retrieved from Scopus (http://www.scopus.com) and from a meta-analysis assessing the relative accuracy of new hrHPV assays versus the standard comparator tests to detect high-grade cervical intraepithelial neoplasia or cancer in primary screening. The cobas 4800 HPV test and Abbott RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas the PapilloCheck HPV-screening test, BD Onclarity HPV assay and the HPV-Risk assay were validated each in one study. Other tests which partially fulfil the 2009 guidelines are the following: Cervista HPV HR Test, GP5+/6+ PCR-LMNX, an in-house E6/E7 RT quantitative PCR and MALDI-TOF (matrix-assisted laser desorption-ionization time-of-flight). The APTIMA HPV assay targeting E6/E7 mRNA of hrHPV was also fully validated. However, the cross-sectional equivalency criteria of the 2009 guidelines were set up for HPV DNA assays. Demonstration of a low risk of CIN3+ after a negative APTIMA test over a longer period is awaited to inform us about its utility in cervical cancer screening at 5-year or longer intervals.

Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study

“…Given the age range of women considered for HPV Faster, they are likely to be largely unaffected by genital warts and there may be merit in offering bivalent vaccine to these women. Retesting the 59 samples in the 1995 cohort that were positive for 16/18 according to the epidemiologically orientated assay with a clinically validated assay (with a cut off set for the detection of CIN2+) 24 , showed that only 7 (4 vaccinated) were HPV 16 positive and none were HPV 18 positive. This suggest that the majority of HPV 16 infection in routinely immunised women may be at thresholds that are clinically irrelevant.…”

Preventive Strategies against Human Papillomaviruses

“…Common methods available for HPV screening are visual examination, cytology-based tests, and a few molecular assays. Although these methods are equally beneficial for detection of HPV in any part of the body, they are commonly practiced for the screening of cervical cancer only [27]. Researchers have also endorsed the implementation of these methods for the screening of HPV in anogenital warts and cancer, oropharyngeal cancer/infection, lung cancer, vaginal, and vulvar or penile cancer.…”

The Value of Partial HPV Genotyping After Conization of Cervical Dysplasias

“…The International Agency for Research on Cancer (IARC) classifies 12 (16,18,31,33,35,39,45, 51, 52, 56, 58 und 59) of the 150 HPV types as class one carcinogens. Genotypes 16 and 18 are among the most common worldwide and are found in over 70 % of squamous cell carcinomas (85 % of CC) and in over 80 % of adenocarcinomas and adenosquamous carcinomas (15 % of CC) [1][2][3][4].…”

“…In addition, the hc2 is the standard against which new HPV test methods are measured; to be regarded as suitable tests non-inferiority to hc2 in terms of clinical sensitivity and specificity must be demonstrated [15,16].…”