Cervical intraepithelial neoplasia or cancer after HPV vaccination: a review of the literature

Main Article Content

Batool H.M. Ali
Jan Blaakær


Introduction. This literature review focuses on examining whether there are studies documenting the emergence of CIN or CC among pre-vaccinated women who were initially HPV naïve, with emphasis on whether genotyping was conducted upon diagnosis.

Methods. This study provides a literature search of available research found in either PubMed or EMBASE. In order to discover relevant studies, the proposed objective is subdivided into blocks to create a search string. In terms of inclusion criteria, the focus is on finding publications that are based on original research, women developing dysplasia or invasive carcinoma after HPV vaccination despite being HPV-naïve at the time of vaccination. The literature search yields four studies in total consisting of two randomized controlled trials, a retrospective cohort and a case-control study.

Results. A total of 1208 cases of HPV infections, CIN or cancer are presented, however only 104 cases are linked to potential vaccination failure. Vaccination failure is associated with various factors such as primary or secondary vaccination failure. However, a definite explanation for why it occurs for each individual cannot be stated with certainty.

Article Details

How to Cite
Cervical intraepithelial neoplasia or cancer after HPV vaccination: a review of the literature. (2024). Danish Journal of Obstetrics and Gynaecology, 2(1), 35-43. https://doi.org/10.56182/djog.v1i1.33

How to Cite

Cervical intraepithelial neoplasia or cancer after HPV vaccination: a review of the literature. (2024). Danish Journal of Obstetrics and Gynaecology, 2(1), 35-43. https://doi.org/10.56182/djog.v1i1.33


Castle PE, Maza M. Prophylactic HPV vaccina-tion: past, present, and future. Epidemiol Infect. 2016 Feb;144(3):449-68. doi: 10.1017/S0950268815002198. Epub 2015 Oct 2. Erratum in: Epidemiol Infect. 2016 Aug;144(11):2472. PMID: 26429676.

Baldur-Felskov B, Dehlendorff C, Junge J, Munk C, Kjaer SK. Incidence of cervical lesions in Danish women before and after implementation of a national HPV vaccination program. Cancer Causes Control. 2014 Jul;25(7):915-22. doi: 10.1007/s10552-014-0392-4. Epub 2014 May 6. PMID: 24797870.

IARC Working Group on the Evaluation of Car-cinogenic Risks to Humans. Human Papilloma-viruses. Lyon (FR): International Agency for Re-search on Cancer; 2007. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 90.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK321760/

Paz-Zulueta M, Álvarez-Paredes L, Rodríguez Díaz JC, Parás-Bravo P, Andrada Becerra ME, Rodríguez Ingelmo JM, Ruiz García MM, Portilla J, Santibañez M. Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade le-sions. BMC Cancer. 2018 Jan 30;18(1):112. doi: 10.1186/s12885-018-4033-2. PMID: 29382323; PMCID: PMC5791190.

Badre-Esfahani S, Larsen MB, Seibæk L, Pe-tersen LK, Blaakær J, Andersen B. Low attend-ance by non-native women to human papillo-mavirus vaccination and cervical cancer screen-ing - A Danish nationwide register-based cohort study. Prev Med Rep. 2020 Apr 28;19:101106. doi: 10.1016/j.pmedr.2020.101106. PMID: 32426214; PMCID: PMC7226879

Badre-Esfahani S, Larsen MB, Seibæk L, Pe-tersen LK, Blaakær J, Støvring H, Andersen B. Non-Adherence To Childhood HPV Vaccination Is Associated With Non-Participation In Cervical Cancer Screening - A Nationwide Danish Regis-ter-Based Cohort Study. Clin Epidemiol. 2019 Nov 8;11:969-980. doi: 10.2147/CLEP.S203023. PMID: 31814770; PMCID: PMC6853196.

Tranberg M, Jensen JS, Bech BH, Blaakær J, Svanholm H, Andersen B. Good concordance of HPV detection between cervico-vaginal self-samples and general practitioner-collected sam-ples using the Cobas 4800 HPV DNA test. BMC Infect Dis. 2018 Jul 27;18(1):348. doi: 10.1186/s12879-018-3254-y. PMID: 30053836; PMCID: PMC6062874.

Tranberg M, Bech BH, Blaakær J, Jensen JS, Svanholm H, Andersen B. HPV self-sampling in cervical cancer screening: the effect of different invitation strategies in various socioeconomic groups - a randomized controlled trial. Clin Epi-demiol. 2018 Aug 23;10:1027-1036. doi: 10.2147/CLEP.S164826. PMID: 30197540; PMCID: PMC6112594.

European Medicines Agency, 2021. Gardasil 9 - European Medicines Agency. [Online] Available at: https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-product-information_en.pdf. [Accessed 28 May 2021].

Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Ces-tero RM, Fedrizzi EN, Hirschberg AL, Mayrand MH, Ruiz-Sternberg AM, Stapleton JT, Wiley DJ, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Cuzick J, Garland SM, Kjaer SK, Bautista OM, Haupt R, Moeller E, Ritter M, Roberts CC, Shields C, Luxembourg A. Final efficacy, immunogenici-ty, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet. 2017 Nov 11;390(10108):2143-2159. doi: 10.1016/S0140-6736(17)31821-4. Epub 2017 Sep 5. PMID: 28886907.

Beachler DC, Kreimer AR, Schiffman M, Her-rero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, Jimenez S, Sa-faeian M, Struijk L, Schussler J, Hildesheim A, Gonzalez P; Costa Rica HPV Vaccine Trial (CVT) Group. Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection. J Natl Cancer Inst. 2015 Oct 14;108(1):djv302. doi: 10.1093/jnci/djv302. PMID: 26467666; PMCID: PMC4862406.

Bogani G, Serati M, Maggiore ULR, Ditto A, Gardella B, Ferrero S, Spinillo A, Ghezzi F, Raspa-gliesi F. Cervical intraepithelial neoplasia in women who had vaccination against HPV. Int J Gynaecol Obstet. 2019 Nov;147(2):233-237. doi: 10.1002/ijgo.12934. Epub 2019 Aug 8. Erratum in: Int J Gynaecol Obstet. 2020 Jan;148(1):133. PMID: 31361908.

Kann H, Hortlund M, Eklund C, Dillner J, Faust H. Human papillomavirus types in cervical dys-plasia among young HPV-vaccinated women: Population-based nested case-control study. Int J Cancer. 2020 May 1;146(9):2539-2546. doi: 10.1002/ijc.32848. Epub 2020 Jan 24. PMID: 31868230.

Dobson SR, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, Langley JM, Bet-tinger JA, Singer J, Money D, Miller D, Naus M, Marra F, Young E. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013 May 1;309(17):1793-802. doi: 10.1001/jama.2013.1625. PMID: 23632723.

Tomljenovic L, Spinosa JP, Shaw CA. Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effec-tive and safe? Curr Pharm Des. 2013;19(8):1466-87. PMID: 23016780.

Garland SM, Brotherton JML, Moscicki AB, Kaufmann AM, Stanley M, Bhatla N, Sankarana-rayanan R, de Sanjosé S, Palefsky JM; IPVS. HPV vaccination of immunocompromised hosts. Pap-illomavirus Res. 2017 Dec;4:35-38. doi: 10.1016/j.pvr.2017.06.002. Epub 2017 Jun 3. PMID: 29179867; PMCID: PMC5883202.

Heininger U, Bachtiar NS, Bahri P, Dana A, Dodoo A, Gidudu J, Santos EM. The concept of vaccination failure. Vaccine. 2012 Feb 8;30(7):1265-8. doi: 10.1016/j.vaccine.2011.12.048. Epub 2011 Dec 21. PMID: 22197579.

Sundhedsstyrelsen (SST), 2020. Sundhedsstyrelsen. [Online] Available at: https://www.sst.dk/da/viden/screening/screening-for-kraeft/livmoderhalskraeft. [Accessed 21 May 2021].

Hammer A, Mejlgaard E, Gravitt P, Høgdall E, Christiansen P, Steiniche T, Blaakaer J. HPV gen-otype distribution in older Danish women un-dergoing surgery due to cervical cancer. Acta Obstet Gynecol Scand. 2015 Nov;94(11):1262-8. doi: 10.1111/aogs.12731. Epub 2015 Sep 12. PMID: 26300424.

Ørnskov D, Jochumsen K, Steiner PH, Grun-net IM, Lykkebo AW, Waldstrøm M. Clinical per-formance and acceptability of self-collected vag-inal and urine samples compared with clinician-taken cervical samples for HPV testing among women referred for colposcopy. A cross-sectional study. BMJ Open. 2021 Mar 5;11(3):e041512. doi: 10.1136/bmjopen-2020-041512. PMID: 33674367; PMCID: PMC7939007.