Primary cervical screening with HPV has now been unambiguously shown to be more effective for cervical cancer prevention than screening with cytology. To ensure that the predicted gains are realized also in the real-life programs, the HPV testing needs to follow similarly stringent quality assurance schemes as other screening methods.
Validation of the methods used needs to be done for every certified laboratory, as the performance of the testing is the product of the assay used and the performance of the laboratory. Clinical validation refers to the sensitivity for detecting specimens with CIN2+ and to the specificity of having a reasonably low proportion of cytology-negative women form the general population testng negative. Analytical validation refers to being able to detect a defined amount of HPV DNA (sensitivity measured in International Units) with low likelyhood of reporting a sample as positive for an HPV type that the sample does not contain (specificity), which could e.g. be due to incorrect typing or contamination.
For clinical validation and quality assurance purposes, large HPV laboratories are systematically saving the cervical samples (biobanking) to be able to perform a clinical validation for sensitivity and specificity if a new test is being considered (1,2). Proficiency panels for analytical validation are available via the HPV LabNet (3).
Quality assurance involves e.g. continuous use of positive and negative controls and monitoring the read outs from these as well as laboratory audit. Audit has been standard practise in most cytology laboratories for decades and is based on identification and re-reading of prior smears from women who later turn out to be diagnosed with cervical cancer or cacinoma in situ. Laboratory audit for HPV uses exactly the same design (identifying archival samples from women who later develop cancer or carcinoma in situ) and subjecting these samples to re-testing and extended testing for detction of rare HPV types or variants (4).
Self-sampling is becoming an increasingly popular strategy to reach in particular non-attending women, but signficantly increases the cost of the screening program. However, theer are now many studies that have used teh same self-sampling kits as are being used for self-sampling for Chlamydia testing also for HPV self-sampling. These reagents are both inexpensive, extensively used and have been foundto produce equally sensitive results (5).
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1. Cervical cytology biobanking in Europe. Arbyn M, Van Veen EB, Andersson K, Bogers J, Boulet G, Bergeron C, von Knebel-Doeberitz M, Dillner J. Int J Biol Markers. 2010 Jul-Sep;25(3):117-25
2. A complex intervention for workflow enhancement at the Swedish cervical cytology biobank. Perskvist N, Björklund C, Dillner J. Biopreserv Biobank. 2014 Feb;12(1):69-73. doi: 10.1089/bio.2013.0
3. Global improvement in genotyping of human papillomavirus DNA: the 2011 HPV LabNet International Proficiency Study. Eklund C, Forslund O, Wallin KL, Dillner J. J Clin Microbiol. 2014 Feb;52(2):449-59. doi: 10.1128/JCM.02453-13.
4. Laboratory audit as part of the quality assessment of a primary HPV-screening program. Hortlund M, Sundström K, Lamin H, Hjerpe A, Dillner J. J Clin Virol. 2016 Feb;75:33-6. doi: 10.1016/j.jcv.2015.12.007.
5. Evaluation of human papillomavirus DNA detection in samples obtained for routine Chlamydia trachomatis screening. Söderlund-Strand A, Wikström A, Dillner J. J Clin Virol. 2015 Mar;64:88-91. doi: 10.1016/j.jcv.2015.01.008