Interlaboratory Reproducibility and Proficiency Testing within the Human Papillomavirus Cervical Cancer Screening Program in Catalonia, Spain

Abstract

P ersistent infection with oncogenic human papillomaviruses (HPVs) is necessary for the development of invasive cervical cancer (CC) (1-3). CC screening based on cervical cytology has been instrumental in decreasing the incidence and mortality associated with CC in those countries with high screening coverage rates (4). However, the infectious etiology of this disease leads to the suggestion that the detection of the DNA of HPVs responsible for cellular transformation might provide a strong predictive marker for the early detection of women at risk (5). Worldwide studies have established that tests for the presence of HPV DNA show a higher sensitivity than cytology for the detection of highgrade cervical intraepithelial lesions (6). Despite this demonstrated higher sensitivity, the application to CC screening programs is still not widespread (6-10).Currently, one of the most widely used tests for the detection of HPV DNA is the Digene Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), approved by the U.S. Food and Drug Administration (FDA) in 2003 for use in clinical settings. Large prospective cohort studies and randomized controlled trials have proved that this assay has high clinical sensitivity (90 to 95%) for the detection of high-grade cervical intraepithelial neoplasia (CIN) (6). The HC2 procedure does not include a PCR amplification step and uses a cocktail of probes designed to detect 13 HPV types classified as carcinogenic (groups 1 and 2A:

Long-term protection of HPV test in women at risk of cervical cancer

“…A positive result was considered if attained or exceeded the FDA-approved threshold of 1.0 relative light unit (RLU/CO). All HPV reference laboratories were part of a quality control with kappa values over 90% [25].…”

Screening of cervical cancer in Catalonia 2006–2012

“…Further, the results of the proficiency testing assessment among laboratories for the HPV test showed that the HC2 assay has a high interlaboratory concordance [ 12 ].…”

“…Every year, 20 samples stratified by different value categories were retested in a different laboratory from the original one. Concordance analyses were performed through the Kappa statistics and by linear regression as detailed elsewhere [ 12 ].…”

“…Finally, for the purpose of monitoring the interlaboratory reproducibility of performance of HPV detection technique, a total of 946 samples were re-tested in a second laboratory during the period 2008–2011. A total of 44 (4.6%) discrepancies were found, and the overall correlation coefficient between the two measurements was 0.95 (p < 0.05) for the continuous evaluation of RLU values, while the kappa value for positive/negative was 0.91, demonstrating an almost excellent interlaboratory agreement for all 12 participating laboratories [ 12 ].…”

“…For this, we estimated the coverage of screening, the interval between cytologies within a first screening round and the rescue of underscreened women. We also evaluated the value of HPV testing as a cotest with cervical cytology in the underscreened women and in the follow-up of women with a diagnosis of atypical squamous cell of undetermined significance (ASC-US) [ 8 – 12 ]. Finally, organisational aspects of the care for sexual and reproductive health centres (ASSIRs) were evaluated.…”