Letter to the Editor

Cervical cancer screening in Switzerland: time to rethink the guidelines

DOI: https://doi.org/10.4414/smw.2015.14112
Publication Date: 09.02.2015
Swiss Med Wkly. 2015;145:w14112

Pierre Vassilakosa, Rosa Catarinob, Brigitte Frey Tirric, Patrick Petignatb

a Geneva Foundation for Medical Education and Research, Geneva, Switzerland
b Department of Gynaecology, Geneva University Hospitals, Switzerland
c Frauenklinik Baselland, Liestal, Switzerland

 

In a previous letter published in Swiss Medical Weekly, we emphasised the need for Switzerland to change from cytology-based to human papillomavirus (HPV) screening for cervical cancer in women aged 30 years and older [1]. According to a recent study published in The Lancet [2], which included individual level data from four randomised controlled trials (RCTs) conducted in Sweden (Swedescreen [3]), the Netherlands (POBASCAM [4, 5]), England (ARTISTIC [6]) and Italy (NTCC [7]), Ronco and colleagues demonstrated that HPV screening is more effective than cytology in preventing cervical cancer. This study had a median follow-up time of 6.5 years and involved more than 175,000 women. As such, it provides a significant milestone for cervical cancer detection based on HPV testing. The authors demonstrated that HPV screening offers 60–70% greater protection against cervical cancer compared with cytology and showed that HPV testing performed at 5-year intervals is safer than a 3-year interval for cytology.

The implications of these findings for cervical cancer prevention are immediate and global, and suggest that international and national experts should now consider how to implement the change from cytology-based to HPV-based screening, as well as an extension of the screening interval. In response to overwhelming evidence from several good-quality RCTs, which demonstrated that HPV testing might be a more clinically effective option [8, 9], some Western countries have already adopted it as a stand-alone cervical cancer screening method. Countries with organised population-based screening programmes where decisions can be executed in a relatively short time period, such as England, the Scandinavian countries and the Netherlands, tend to embrace the change more easily than countries not having a well-controlled screening system. Indeed, the Netherlands have already entered the annals of public health history as a pioneer in the implementation of an HPV-based cervical cancer screening protocol [10].

Reluctance to accept the change may come from physicians who consider Pap smears to be part of every woman’s annual visit; if intervals for screening are lengthened, they fear that women will not come for an annual check-up and may be less inclined to undergo screening. Price is another important concern, and efforts should be made to ensure that HPV testing is fully refunded by health insurance, as is the case for Pap smears. Concerns about the introduction of HPV testing have to be balanced by societal and epidemiological perspectives, because the best strategy for preventing cervical cancer is to use the most accurate test (maximising the benefits of screening) at the longest possible interval (minimising the potential harm of screening). However, Western countries, with liberal health systems and opportunistic screening depending on the initiative of individual women and physicians, have demonstrated in the history of cervical cancer prevention that, despite the presence of a general agreement in favour of new recommendations, the speed and scope of clinical adoption might greatly vary. This is particularly true because each interest group has its own directives and limitations.

The United States of America was the first country with opportunistic screening to recommend HPV testing. Since 2012, the American College of Obstetricians and Gynecologists and the American Cancer Society have recommended that women aged 30–65 years should undergo “co-testing” with both cytology screening and HPV testing every 5 years if both tests are negative [11]. In fact, HPV testing alone is not recommended. However, this recommendation might be about to change, because the US Food and Drug Administration has approved (on April 24 2014) HPV testing as a first-line screening method for cervical cancer screening [12].

In the case of Switzerland, it is now time to incorporate HPV testing in the national cervical cancer screening recommendation and to update the current guidelines. Evidence suggests that longer screening intervals would be appropriate for HPV testing owing to its high negative predictive value. Furthermore, the extension of the screening interval controls overscreening and reduces the detection of transient HPV infections and insignificant lesions, thus minimising the risk of undergoing unnecessary procedures.

Besides the evidence provided by Ronco et al. [2], Elfstrom et al. [13] analysed data from a RCT on HPV testing in Sweden (13 years of follow-up) and found the longitudinal sensitivity of cytology in the control arm at 3 years (85.9%, 95% confidence interval [CI] 76.9–91.8) to be similar to the sensitivity of HPV testing in the intervention arm at 5 years (86.4%, 95% CI 79.2–91.4). Their results support an HPV screening interval of 5 years. Other previous cohort studies equally suggest that screening intervals of 5 years may be appropriate [14–16]. Subsequently, European [10] and recently Australian authorities [17] suggest that HPV screening can be safely implemented with at least a 5-year interval.

Nevertheless, it should be stressed that 5-year cervical screening using HPV testing should be implemented preferably within a population-based screening programme with a call and recall system, which Switzerland has yet to establish.

HPV testing has mediocre specificity and positive predictive value for cervical cancer screening. A triage involving cytology and genotyping would alleviate this issue by identifying high-risk HPV-positive women at highest risk for cancer [18]. Therefore, HPV testing is generally recommended for women aged 30 to 65 years. For women under 30 years, a screening recommendation providing the best balance of benefits and harms should be introduced.

Finally, the choice of the HPV test to be used should be based on cost-effectiveness and clinical validation as recommended by Meijer et al. [19].

In conclusion, since the introduction of the Pap smear 60 years ago, the incidence of cervical cancer has declined by almost 60%, becoming a major public health success in Switzerland and other Western countries, and being adopted as standard practice. Nevertheless, we now have strong evidence that HPV testing is more effective than cytology for cervical cancer screening, providing increased reassurance and allowing longer screening intervals to be adopted. These data support the transition from a good test (a frequent Pap smear) to a better one (less frequent HPV testing) that is both cost-effective and safer for women. These changes should be accompanied with accurate and unbiased information about benefits and associated risks of an HPV-based screening, which should be given to all women, so they can make an informed choice about cervical cancer screening.

Correspondence

Correspondence: Rosa Catarino, MD, Department of Gynaecology and Obstetrics, Geneva University Hospitals, Boulevard de la cluse 30, CH-1211 Geneva (Geneva), Switzerland, rosapintocatarino[at]gmail.com

References

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  2 Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, et al; International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524–32.

  3 Naucler P, Ryd W, Törnberg S, Strand A, Wadell G, Elfgren K, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med. 2007;357(16):1589–97.

  4 Bulkmans N, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, et al. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet. 2007;370(9601):1764–72.

  5 Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012;13(1):78–88.

  6 Kitchener HC, Almonte M, Thomson C, Wheeler P, Sargent A, Stoykova B, et al. HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol. 2009;10(7):672–82.

  7 Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010;11(3):249–57.

  8 Murphy J, Kennedy EB, Dunn S, McLachlin CM, Fung Kee Fung M, Gzik D, et al. HPV testing in primary cervical screening: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2012;34(5):443–52.

  9 Arbyn M, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30:F88–F99.

10 Health Council of the Netherlands. Population screening for cervical cancer. http://www.gezondheidsraad.nl/en/publications/prevention/population-screening-cervical-cancer (2011) (accessed April 28, 2014).

11 Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62(3):147–72.

12 U.S. Food and Drug Administration (FDA). FDA approves first human papillomavirus test for primary cervical cancer screening. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394773.htm. (accessed April 24, 2014).

13 Elfström KM, Smelov V, Johansson AL, Eklund C, Nauclér P, Arnheim-Dahlström L, et al. Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. BMJ. 2014;348.

14 Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008;337.

15 Katki HA, Kinney WK, Fetterman B, Lorey T, Poitras NE, Cheung L, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol. 2011;12(7):663–72.

16 Kitchener HC, Gilham C, Sargent A, Bailey A, Albrow R, Roberts C, et al. A comparison of HPV DNA testing and liquid based cytology over three rounds of primary cervical screening: extended follow up in the ARTISTIC trial. Eur J Cancer. 2011;47(6):864–71.

17 Australian Government. MSCA. Application No. 1276 – Renewal of the National Cervical Screening Program. (2014, April 3–4). Retrieved November 4, 2014, from http://www.msac.gov.au/internet/msac/publishing.nsf/Content/FD36D6990FFAA639CA25799200058940/$File/1276%20–%20Final%20MSAC%20PSD%20–%20NCSP%20Renewal.pdf http://www.msac.gov.au/internet/msac/publishing.nsf/Content/FD36D6990FFAA639CA25799200058940/$File/1276 – Final MSAC PSD – NCSP Renewal.pdf .

18 Naucler P, Ryd W, Törnberg S, Strand A, Wadell G, Elfgren K, et al. Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening. J Natl Cancer Inst. 2009;101(2):88–99.

19 Meijer CJ, Berkhof J, Castle PE, Hesselink AT, Franco EL, 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. 2009;124(3):516–20.

 

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