Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study

Background: In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy.

Patients And Methods: This is an observational prospective cohort study performed in 7 academic Obstetrics and Gynaecology Departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected.

Results: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated.

Conclusion: HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.

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References

Palmer T, Wallace L, Pollock K, Cuschieri K, Robertson C, Kavanagh K . Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ. 2019; 365:l1161. PMC: 6446188. DOI: 10.1136/bmj.l1161. View

Kalliala I, Athanasiou A, Veroniki A, Salanti G, Efthimiou O, Raftis N . Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature. Ann Oncol. 2020; 31(2):213-227. PMC: 7479506. DOI: 10.1016/j.annonc.2019.11.004. View

Laara E, Day N, Hakama M . Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet. 1987; 1(8544):1247-9. DOI: 10.1016/s0140-6736(87)92695-x. View

Szarewski A, Poppe W, Skinner S, Wheeler C, Paavonen J, Naud P . Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18. Int J Cancer. 2011; 131(1):106-16. DOI: 10.1002/ijc.26362. View

Ault K . Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol. 2006; 2006 Suppl:40470. PMC: 1581465. DOI: 10.1155/IDOG/2006/40470. View

Gakidou E, Nordhagen S, Obermeyer Z . Coverage of cervical cancer screening in 57 countries: low average levels and large inequalities. PLoS Med. 2008; 5(6):e132. PMC: 2429949. DOI: 10.1371/journal.pmed.0050132. View

Hall M, Simms K, Lew J, Smith M, Brotherton J, Saville M . The projected timeframe until cervical cancer elimination in Australia: a modelling study. Lancet Public Health. 2018; 4(1):e19-e27. DOI: 10.1016/S2468-2667(18)30183-X. View

Bruni L, Diaz M, Barrionuevo-Rosas L, Herrero R, Bray F, Bosch F . Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis. Lancet Glob Health. 2016; 4(7):e453-63. DOI: 10.1016/S2214-109X(16)30099-7. View

Kyrgiou M, Mitra A, Arbyn M, Stasinou S, Martin-Hirsch P, Bennett P . Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ. 2014; 349:g6192. PMC: 4212006. DOI: 10.1136/bmj.g6192. View

10.

Argyri E, Tsimplaki E, Papatheodorou D, Daskalopoulou D, Panotopoulou E . Recent Trends in HPV Infection and Type Distribution in Greece. Anticancer Res. 2018; 38(5):3079-3084. DOI: 10.21873/anticanres.12565. View

11.

Stasinou S, Valasoulis G, Kyrgiou M, Malamou-Mitsi V, Bilirakis E, Pappa L . Large loop excision of the transformation zone and cervical intraepithelial neoplasia: a 22-year experience. Anticancer Res. 2012; 32(9):4141-5. View

12.

Arbyn M, Xu L, Simoens C, Martin-Hirsch P . Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018; 5:CD009069. PMC: 6494566. DOI: 10.1002/14651858.CD009069.pub3. View

13.

Arbyn M, Redman C, Verdoodt F, Kyrgiou M, Tzafetas M, Ghaem-Maghami S . Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol. 2017; 18(12):1665-1679. DOI: 10.1016/S1470-2045(17)30700-3. View

14.

Kyrgiou M, Mitra A, Arbyn M, Paraskevaidi M, Athanasiou A, Martin-Hirsch P . Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2015; (9):CD008478. PMC: 6457639. DOI: 10.1002/14651858.CD008478.pub2. View

15.

Paraskevaidis E, Koliopoulos G, Malamou-Mitsi V, Zikopoulos K, Paschopoulos M, Pappa L . Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience. Anticancer Res. 2001; 21(4B):3097-9. View

16.

Guedes A, Zeferino L, Syrjanen K, Brenna S . Short-term outcome of cervical intraepithelial neoplasia grade 2: considerations for management strategies and reproducibility of diagnosis. Anticancer Res. 2010; 30(6):2319-23. View

17.

Tainio K, Athanasiou A, Tikkinen K, Aaltonen R, Cardenas J, Hernandes . Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018; 360:k499. PMC: 5826010. DOI: 10.1136/bmj.k499. View

18.

Westra T, Rozenbaum M, Rogoza R, Nijman H, Daemen T, Postma M . Until which age should women be vaccinated against HPV infection? Recommendation based on cost-effectiveness analyses. J Infect Dis. 2011; 204(3):377-84. DOI: 10.1093/infdis/jir281. View

19.

Kang W, Choi H, Kim S . Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)?. Gynecol Oncol. 2013; 130(2):264-8. DOI: 10.1016/j.ygyno.2013.04.050. View

20.

Gustafsson L, Ponten J, Bergstrom R, Adami H . International incidence rates of invasive cervical cancer before cytological screening. Int J Cancer. 1997; 71(2):159-65. DOI: 10.1002/(sici)1097-0215(19970410)71:2<159::aid-ijc6>3.0.co;2-#. View