The impact of cervical cancer screening for different HPV genotypes
Quote this article as:
J Wang et al. (June 2024). The impact of cervical cancer screening for different HPV genotypes. www.HPVWorld.com, 264
It has been known for decades that different oncogenic HPV types have different prevalences1 and differ greatly in their oncogenicity2,3. However, it is only in recent years that several HPV screening platforms that include an automatic, extended genotyping have become available4. While the impact of screening for a particular HPV type is intuitively dependent on population prevalence and HPV type oncogenicity, it is also affected by how effective the screening can be in preventing cervical cancer cases caused by different HPV types. A comprehensive assessment integrating these factors may help a screening program to plan and adjust the strategy by HPV type.
We linked the Swedish national registers of cervical screening and cervical cancer in the entire Swedish population of 3.6 million women, as well as data from population-based randomized trials and HPV genotyping of cervical cancers in the entire country in 10 years5. These data provided HPV type-specific prevalences in the population, and HPV type distribution in cervical cancer cases in relation to their complete screening histories 10 years prior to cancer diagnosis. We integrated this information on HPV type-specific prevalences, oncogenicity and screening effectiveness, and estimated the impact numbers for each HPV type:
- Number needed to screen (NNS) refers to the number of women who need to be screened to prevent (or detect) one case of cervical cancer.
- Number needed to follow up (NNF) refers to how many screen-positive women need to be followed up in order to prevent (or detect) one case of cervical cancer.
As expected, the impact numbers differ greatly across HPV types. HPV 16 has the lowest NNS and NNF, which indicates that HPV16 is the HPV type with the highest effectiveness and efficiency to screen for: one case of HPV16-caused cervical cancer is prevented for every 5,527 women attending screening. Prevention of one case of HPV16-caused cervical cancer required a follow-up of 147 HPV16-positive women. The NNS and NNF were up to 40 to 500 times higher for the HPV types commonly screened for with lower oncogenic potential (HPV35,39,51,56,59,66,68), suggesting lower screening efficiency (Table 1).
The cross-type variation is particularly large among young women under age 30 years: for the types with lower oncogenic potential, preventing one case of cervical cancer would require screening of >220,000 women and following up >16,000 screen-positive women, an effort that can be considered as unreasonably large (Figure 1).
Impact numbers may vary across different settings and populations due to variations in HPV type-specific prevalences, and therefore they can be re-calculated in populations with substantially different type-specific HPV prevalence. HPV vaccination will change dramatically the HPV type-specific prevalences in the young population: NNS of vaccination types will increase when vaccine coverage is high, meanwhile, the NNS and NNF of non-vaccination types will continue to be very high. Consequently, the screening strategy in young women should be adjusted. Since the impact numbers shown in this study were calculated from the unvaccinated population, we are currently monitoring the change of impact numbers in the young birth cohorts in Sweden in order to provide an evidence base for optimizing screening strategies.
Although there have been major advances in scientific evidence, cervical screening policies have changed only slowly. The aetiology discovery of HPV was 40 years ago. The knowledge that different HPV types have different risks and the development of HPV screening tests happened already several decades ago. Rapid changes in the screening strategy are expected in the near future in terms of self-tests, accurate and automated triage tests, and adjustments to the vaccinated population. Hopefully, using impact numbers of screening for different HPV types will help comparing, designing and adapting efficient screening strategies over time.
DISCLOSURE
The Authors declare no conflict of interests to disclose.
This research work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No.847845 (Project RISCC).
References
1. de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007;7:453–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(07)70158-5.
2. IARC. Cervical Cancer Screening: IARC Handbooks of Cancer Prevention Volume 18. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Handbooks-Of-Cancer-Prevention/Cervical-Cancer-Screening-2022.
3. Combes J-D, Guan P, Franceschi S, Clifford GM. Judging the carcinogenicity of rare human papillomavirus types. Int J Cancer. 2015;136:740–742. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ijc.29019.
4. Arbyn M, Simon M, Peeters E, Xu L, Meijer CJLM, Berkhof J, et al. 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clin Microbiol Infect. 2021;27:1083–95. Available from: https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00219-6/fulltext.
5. Wang J, Elfström KM, Lagheden C, Eklund C, Sundström K, Sparén P, et al. Impact of cervical screening by human papillomavirus genotype: Population-based estimations. PLOS Med. 2023;20: e1004304. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637721/pdf/pmed.1004304.pdf.
This article is included in the HPW monograph Cervical cancer prevention in Europe
Scientific coordinators:
Johannes Berkhof, Kate Cuschieri, Clàudia Robles, Xavier Bosch
HPW editors:
Patricia Guijarro, Paula Peremiquel, Valentina Rangel
On behalf of the editorial team, we would like to thank all the authors who contributed to this special HPW monograph
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