This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising.
Subscribe to Journal
Get full journal access for 1 year
only $20.79 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386 (2015).
IARC. Cervix cancer screening, Vol 10 (IARC, Lyon, 2005).
CancerResearchUK. Cervical cancer incidence statistics. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cervical-cancer/incidence. (2015).
Anttila, A. & Nieminen, P. Cervical cancer screening programme in Finland with an example on implementing alternative screening methods. Coll. Antropol. 31(Suppl 2), 17–22 (2007).
NICE. Guidance on the use of liquid-based cytology for cervical screening. http://www.nice.org.uk (2003).
Arbyn, M., Bergeron, C., Klinkhamer, P., Martin-Hirsch, P., Siebers, A. G. & Bulten, J. Liquid compared with conventional cervical cytology: a systematic review and meta-analysis. Obstet. Gynecol. 111, 167–177 (2008).
Insinga, R. P., Glass, A. G. & Rush, B. B. Diagnoses and outcomes in cervical cancer screening: a population-based study. Am. J. Obstet. Gynecol. 191, 105–113 (2004).
Arbyn, M., Anttila, A., Jordan, J., Ronco, G., Schenck, U., Segnan, N. et al. European Guidelines for Quality Assurance in Cervical Cancer Screening. Second edition-summary document. Ann. Oncol. 21, 448–458 (2010).
Ronco, G., Dillner, J., Elfstrom, K. M., Tunesi, S., Snijders, P. J., Arbyn, M. et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 383, 524–532 (2014).
Koliopoulos, G., Arbyn, M., Martin-Hirsch, P., Kyrgiou, M., Prendiville, W., Paraskevaidis, E. Diagnostic accuracy of human papillomavirus testing in primary cervical screening: a systematic review and meta-analysis of non-randomized studies. Gynecol Oncol. 104, 232–246 (2007).
Torres, K. L., Marino, J. M., Pires Rocha, D. A., de Mello, M. B., de Melo Farah, H. H., Reis, R., D. S et al. Self-sampling coupled to the detection of HPV 16 and 18 E6 protein: A promising option for detection of cervical malignancies in remote areas. PLoS ONE 13, e0201262 (2018).
Cuzick, J., Clavel, C., Petry, K. U., Meijer, C. J., Hoyer, H., Ratnam, S. et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int. J. Cancer 119, 1095–1101 (2006).
Arbyn, M., Ronco, G., Anttila, A., Meijer, C. J., Poljak, M., Ogilvie, G. et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 30, F88–F99 (2012).
Ogilvie, G. S., van Niekerk, D., Krajden, M., Smith, L. W., Cook, D., Gondara, L. et al. Effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: the HPV FOCAL Randomized Clinical Trial. JAMA 320, 43–52 (2018).
Sankaranarayanan, R., Nene, B. M., Shastri, S. S., Jayant, K., Muwonge, R., Budukh, A. M. et al. HPV screening for cervical cancer in rural India. N. Engl. J. Med. 360, 1385–1394 (2009).
O’Connor, M., O’Leary, E., Waller, J., Gallagher, P., Martin, C. M., O’Leary, J. J. et al. Socio-economic variations in anticipated adverse reactions to testing HPV positive: implications for the introduction of primary HPV-based cervical screening. Preventive Med. 115, 90–96 (2018).
Arbyn, M., Verdoodt, F., Snijders, P. J., Verhoef, V. M., Suonio, E., Dillner, L. et al. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 15, 172–183 (2014).
Arbyn, M., Smith, S. B., Temin, S., Sultana, F. & Castle, P. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ 363, k4823 (2018).
von Karsa, L., Arbyn, M., De Vuyst, H., Dillner, J., Dillner, L., Franceschi, S. et al. European guidelines for quality assurance in cervical cancer screening. Summary of the supplements on HPV screening and vaccination. Papillomavirus Res. 1, 22–31 (2015).
Poljak, M. & Kocjan, B. J. Commercially available assays for multiplex detection of alpha human papillomaviruses. Expert Rev. Anti Infect. Ther. 8, 1139–1162 (2010).
Poljak, M., Cuzick, J., Kocjan, B. J., Iftner, T., Dillner, J. & Arbyn, M. Nucleic acid tests for the detection of alpha human papillomaviruses. Vaccine 30(Suppl 5), F100–F106 (2012).
Poljak, M., Kocjan, B. J., Ostrbenk, A. & Seme, K. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update. J. Clin. Virol. 76(Suppl 1), S3–s13 (2016).
Arbyn, M., Snijders, P. J., Meijer, C. J., Berkhof, J., Cuschieri, K., Kocjan, B. J. et al. Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin. Microbiol. Infect. 21, 817–826 (2015).
Meijer, C. J., Berkhof, J., Castle, P. E., Hesselink, A. T., Franco, E. L., Ronco, G. et al. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. Int. J. Cancer 124, 516–520 (2009).
Ronco, G., Arbyn, M., Meijer, C. J. L. M., Snijders, P. J. F., Cuzick, J. Screening for Cervical Cancer with Primary Testing for Human Papillomavirus (Supplement 1), 2nd edn (Office for Official Publications of the European Union, Luxembourg, 2015).
Wheeler, C. M., Hunt, W. C., Cuzick, J., Langsfeld, E., Pearse, A., Montoya, G. D. et al. A population-based study of human papillomavirus genotype prevalence in the United States: baseline measures prior to mass human papillomavirus vaccination. Int. J. Cancer 132, 198–207 (2013).
Cuzick, J. & Wheeler, C. Need for expanded HPV genotyping for cervical screening. Papillomavirus Res. 2, 112–115 (2016).
Aro, K., Nieminen, P., Louvanto, K., Jakobsson, M., Virtanen, S., Lehtinen, M. et al. Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women. Gynecol. Oncol. 154, 354–359 (2019).
Massad, L. S., Einstein, M. H., Huh, W. K., Katki, H. A., Kinney, W. K., Schiffman, M. et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J. Low. Genit. Trac. Dis. 17, S1–s27 (2013).
Rebolj, M., Rimmer, J., Denton, K., Tidy, J., Mathews, C., Ellis, K. et al. Primary cervical screening with high risk human papillomavirus testing: observational study. BMJ 364, l240 (2019).
Tsoumpou, I., Arbyn, M., Kyrgiou, M., Wentzensen, N., Koliopoulos, G., Martin-Hirsch, P. et al. p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 35, 210–220 (2009).
Tsoumpou, I., Valasoulis, G., Founta, C., Kyrgiou, M., Nasioutziki, M., Daponte, A. et al. High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a prospective diagnostic study. Gynecol Oncol. 121, 49–53 (2011).
Ronco, G., Giorgi-Rossi, P., Carozzi, F., Confortini, M., Dalla Palma, P., Del Mistro, A. et al. Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test. J. Natl Cancer Inst. 100, 492–501 (2008).
Wright, T. C. Jr, Behrens, C. M., Ranger-Moore, J., Rehm, S., Sharma, A., Stoler, M. H. et al. Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: results from a sub-study nested into the ATHENA trial. Gynecol. Oncol. 144, 51–56 (2017).
Ikenberg, H., Bergeron, C., Schmidt, D., Griesser, H., Alameda, F., Angeloni, C. et al. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J. Natl Cancer Inst. 105, 1550–1557 (2013).
Luttmer, R., De Strooper, L. M., Berkhof, J., Snijders, P. J., Dijkstra, M. G., Uijterwaal, M. H. et al. Comparing the performance of FAM19A4 methylation analysis, cytology and HPV16/18 genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive women of a gynecologic outpatient population (COMETH study). Int. J. Cancer 138, 992–1002 (2016).
Lorincz, A. T., Brentnall, A. R., Vasiljevic, N., Scibior-Bentkowska, D., Castanon, A., Fiander, A. et al. HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology. Int. J. Cancer 133, 637–644 (2013).
Louvanto, K., Aro, K., Nedjai, B., Butzow, R., Jakobsson, M., Kalliala, I., et al. Methylation in predicting progression of untreated high-grade cervical intraepithelial neoplasia. Clin. Infect. Dis. pii: ciz677. (2019).
Gravitt, P. E., Kovacic, M. B., Herrero, R., Schiffman, M., Bratti, C., Hildesheim, A. et al. High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. Int. J. Cancer 121, 2787–2793 (2007).
Xi, L. F., Hughes, J. P., Castle, P. E., Edelstein, Z. R., Wang, C., Galloway, D. A. et al. Viral load in the natural history of human papillomavirus type 16 infection: a nested case-control study. J. Infect. Dis. 203, 1425–1433 (2011).
Fu, Xi,L., Schiffman, M., Ke, Y., Hughes, J. P., Galloway, D. A., He, Z. et al. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18. Int. J. Cancer 140, 1747–1756 (2017).
Vasiljevic, N., Carter, P. D., Reuter, C., Warman, R., Brentnall, A. R., Carton, J. R. et al. Role of quantitative p16(INK4A) mRNA assay and digital reading of p16(INK4A) immunostained sections in diagnosis of cervical intraepithelial neoplasia. Int. J. Cancer 141, 829–836 (2017).
Coleman, D., Day, N., Douglas, G., Farmery, E., Lynge, E., Philip, J. et al. European Guidelines for Quality Assurance in Cervical Cancer Screening. Europe against cancer programme. Eur. J. Cancer 29A(Suppl 4), S1–S38 (1993).
Mendes, D., Bains, I., Vanni, T. & Jit, M. Systematic review of model-based cervical screening evaluations. BMC Cancer 15, 334 (2015).
Goldhaber-Fiebert, J. D., Stout, N. K., Salomon, J. A., Kuntz, K. M. & Goldie, S. J. Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16,18 vaccination. J. Natl Cancer Inst. 100, 308–320 (2008).
Huh, W. K., Williams, E., Huang, J., Bramley, T. & Poulios, N. Cost effectiveness of human papillomavirus-16/18 genotyping in cervical cancer screening. Appl. Health Econ. Health Policy 13, 95–107 (2015).
Kim, J. J., Burger, E. A., Sy, S., Campos, N. G. Optimal cervical cancer screening in women vaccinated against human papillomavirus. J. Natl Cancer Inst. 109, djw216 (2016).
Lew, J. B., Simms, K. T., Smith, M. A., Hall, M., Kang, Y. J., Xu, X. M. et al. Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program. Lancet Public Health 2, e96–e107 (2017).
de Kok, I. M., van Rosmalen, J., Dillner, J., Arbyn, M., Sasieni, P., Iftner, T. et al. Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model. BMJ 344, e670 (2012).
de Kok, I., Korfage, I. J., van den Hout, W. B., Helmerhorst, T. J. M., Habbema, J. D. F., Essink-Bot, M. L. et al. Quality of life assumptions determine which cervical cancer screening strategies are cost-effective. Int. J. Cancer 142, 2383–2393 (2018).
Palmer, T., Wallace, L., Pollock, K. G., Cuschieri, K., Robertson, C., Kavanagh, K. et al. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ 365, l1161 (2019).
Mesher, D., Panwar, K., Thomas, S. L., Edmundson, C., Choi, Y. H., Beddows, S. et al. The impact of the National HPV Vaccination Program in England using the bivalent HPV vaccine: surveillance of type-specific HPV in young females, 2010–2016. J. Infect. Dis. 218, 911–921 (2018).
Ferris, D. G., Samakoses, R., Block, S. L., Lazcano-Ponce, E., Restrepo, J. A., Mehlsen, J., et al. 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents after 10 years. Pediatrics 140, e20163947 (2017).
Schwarz, T. F., Galaj, A., Spaczynski, M., Wysocki, J., Kaufmann, A. M., Poncelet, S. et al. Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15–55 years of age. Cancer Med. 6, 2723–2731 (2017).
Pedersen, K., Burger, E. A., Nygård, M., Kristiansen, I. S. & Kim, J. J. Adapting cervical cancer screening for women vaccinated against human papillomavirus infections: the value of stratifying guidelines. Eur. J. Cancer 91, 68–75 (2018).
Giorgi Rossi, P., Carozzi, F., Federici, A., Ronco, G., Zappa, M. & Franceschi, S. Cervical cancer screening in women vaccinated against human papillomavirus infection: recommendations from a consensus conference. Prev. Med. 98, 21–30 (2017).
Landy, R., Windridge, P., Gillman, M. S. & Sasieni, P. D. What cervical screening is appropriate for women who have been vaccinated against high risk HPV? A simulation study. Int. J. Cancer 142, 709–718 (2018).
Pollock, K. G., Kavanagh, K., Potts, A., Love, J., Cuschieri, K., Cubie, H. et al. Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. Br. J. Cancer 111, 1824–1830 (2014).
Guan, P., Howell-Jones, R., Li, N., Bruni, L., de Sanjosé, S., Franceschi, S. et al. Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer. Int. J. Cancer 131, 2349–2359 (2012).
Franco, E. L., Mahmud, S. M., Tota, J., Ferenczy, A. & Coutlee, F. The expected impact of HPV vaccination on the accuracy of cervical cancer screening: the need for a paradigm change. Arch. Med. Res. 40, 478–485 (2009).
Castle, P. E., Stoler, M. H., Wright, T. C. Jr., Sharma, A., Wright, T. L. & Behrens, C. M. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 12, 880–890 (2011).
HealthCouncil. Screening for cervical cancer [Screening op baarmoederhalskanker], Vol 2011/07 (Health Council, Den Haag, 2011).
Kitchener, H. C., Canfell, K., Gilham, C., Sargent, A., Roberts, C., Desai, M. et al. The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds. Health Technol. Assess. 18, 1–196 (2014).
Bains, I., Choi, Y. H., Soldan, K., Jit, M. Clinical impact and cost-effectiveness of primary cytology versus human papillomavirus testing for cervical cancer screening in England. Int. J. Gynecol. Cancer ijgc-2018-000161 (2019).
Gultekin, M., Zayifoglu Karaca, M., Kucukyildiz, I., Dundar, S., Boztas, G., Semra Turan, H. et al. Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women. Int. J. Cancer 142, 1952–1958 (2018).
Ronco, G., Biggeri, A., Confortini, M., Naldoni, C., Segnan, N., Sideri, M. et al. [Health technology assessment report: HPV DNA based primary screening for cervical cancer precursors]. Epidemiol. Prev. 36, e1–e72 (2012).
Ronco, G., Giorgi Rossi, P., Giubilato, P., Del Mistro, A., Zappa, M. & Carozzi, F. A first survey of HPV-based screening in routine cervical cancer screening in Italy. Epidemiol. Prev. 39, 77–83 (2015).
Ronco, G., Zappa, M., Franceschi, S., Tunesi, S., Caprioglio, A., Confortini, M. et al. Impact of variations in triage cytology interpretation on human papillomavirus-based cervical screening and implications for screening algorithms. Eur. J. Cancer 68, 148–155 (2016).
European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC).
Ethics approval and consent to participate
Consent to publish
All authors have given consent to publish.
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.
F.X.B. has received institutional research and educational support from Hologic and MSD and personal support from MSD, Hologic and Seegen for traveling and speaking at medical symposiums; M.G. has received personal support from MSD for traveling and speaking at medical symposiums; M.K. has received institutional research and educational support from MSD and personal support from MSD and Hologic for traveling and speaking at medical symposiums. The rest report no conflict of interest. MA’s institution received funding from the European Society of Gynaecological Oncology, the European Federation for Colposcopy and the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (grant no. 847845). J.C. is an editorial board member of the BJC.
There was no funding.
Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Kyrgiou, M., Arbyn, M., Bergeron, C. et al. Cervical screening: ESGO-EFC position paper of the European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC). Br J Cancer 123, 510–517 (2020). https://doi.org/10.1038/s41416-020-0920-9
The Lancet Public Health (2020)