The efficacy of human papillomavirus vaccination in the prevention of recurrence of severe cervical lesions

Czech version

Authors: B. Sehnal ¹; T. Pichlík ¹; M. J. Halaška ¹; M. Větrovská ¹; A. Babková ¹; J. Drozenová ²; H. Robová ¹; L. Rob ¹
Authors‘ workplace: Onkogynekologické centrum, Gynekologicko-porodnická klinika 3. LF UK FNKV, Praha ¹; Ústav patologie, 3. LF UK FNKV, Praha ²
Published in: Ceska Gynekol 2023; 88(4): 294-300
Category:
doi: https://doi.org/10.48095/cccg2023294

Overview

Objective: A review of current knowledge on the efficacy of human papillomavirus (HPV) vaccination in preventing recurrent severe cervical lesions after excisional surgical treatment. Methods and results: HPV infection is necessary for the development of most cervical precancerous lesions and cervical cancers. Currently, three prophylactic vaccines against HPV infection are available on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. All three prophylactic vaccines show high effect in preventing the development of precancerous lesions. The highest efficacy is achieved in the HPV naive population. The surgical excision of severe cervical precancers is the standard approach. However, guidelines regarding HPV vaccination at the time of conisation are not clearly determined. Women diagnosed with severe cervical lesions have mostly not been vaccinated against HPV so far. Therefore, it is beneficial to understand the importance and efficacy of HPV vaccination at the time of conisation in preventing recurrent precancerous lesions. The exact value of HPV vaccination in the context of surgical excision of precancerous lesions remains unclear, but vaccination is definitely valuable in reducing the risk of recurrence. Vaccination timing seems to be more favorable before surgery. However, the ideal timing of vaccination is not established. Some of these questions are likely to be answered by the results of ongoing randomized controlled trials. Conclusion: Adjuvant HPV vaccination in the setting of surgical treatment for cervical precancerous lesion is significantly associated with a reduced risk of recurrence. HPV vaccination should be strongly considered as adjuvant therapy, especially in young patients undergoing conisation for a severe cervical lesion.

Keywords:

vaccination – human papillomavirus – efficacy – HPV vaccine – cervical precancerosis – recurrent cervical dysplasia

Sources

1. Giuliano AR, Nyitray AG, Kreimer AR et al. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer 2015; 136 (12): 2752–2760. doi: 10.1002/ijc.29082.

2. Sehnal B, Driák D, Nipčová Džubáková M et al. Aktuální data o účinnosti HPV vakcinace v primární prevenci cervikálních lézí. Ceska Gynekol 2022; 87 (2): 124–130. doi: 10.48095/cccg 2022124.

3. Hildesheim A, Gonzalez P, Kreimer AR et al. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obstet Gynecol 2016; 215 (2): 212.e1–212.e15. doi: 10.1016/j.ajog.2016.02.021.

4. Tjalma WA, van Heerden J, Van den Wyngaert T. If prophylactic HPV vaccination is considered in a woman with CIN2+, what is the value and should it be given before or after the surgical treatment? Eur J Obstet Gynecol Reprod Biol 2022; 269: 98–101. doi: 10.1016/ j.ejogrb.2021. 11.008.

5. Garland SM, Paavonen J, Jaisamrarn U et al. Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: post-hoc analysis from a randomized controlled trial. Int J Cancer 2016; 139 (2): 2812–2826. doi: 10.1002/ijc.30 391.

6. Sand FL, Kjaer SK, Frederiksen K et al. Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status. Int J Cancer 2020; 147 (3): 641–647. doi: 10.1002/ijc.32752.

7. Arbyn M, Xu L, Simoens C et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018; 5 (5): CD009069. doi: 10.1002/14651858.CD009069.pub3.

8. Casajuana-Pérez A, Ramírez-Mena M, Ruipérez-Pacheco E et al. Effectiveness of prophylactic human papillomavirus vaccine in the prevention of recurrence in women conized for HSIL/CIN2–3: the VENUS study. Vaccines (Basel) 2022; 10 (2): 288. doi: 10.3390/vaccines10020288.

9. Garland SM, Paavonen J, Jaisamrarn U et al. HPV PATRICIA Study Group. Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: post-hoc analysis from a randomized controlled trial. Int J Cancer 2016; 139 (12): 2812–2826. doi: 10.1002/ijc.30391.

10. Joura EA, Garland SM, Paavonen J et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: Retrospective pooled analysis of trial data. BMJ 2012; 344: e1401. doi: 10.1136/bmj.e1401.

11. Kang WD, Choi HS, Kim SM. 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): 264–268. doi: 10.1016/j.ygyno.2013.04.050.

12. Di Donato V, Caruso G, Petrillo M et al. Adjuvant HPV vaccination to prevent recurrent cervical dysplasia after surgical treatment: a meta--analysis. Vaccines (Basel) 2021; 9 (5): 410. doi: 10.3390/vaccines9050410.

13. Eriksen DO, Jensen PT, Schroll JB et al. Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2022; 101 (6): 597–607. doi: 10.1111/aogs.14359.

14. Lichter K, Krause D, Xu J et al. Adjuvant human papillomavirus vaccine to reduce recurrent cervical dysplasia in unvaccinated women: a systematic review and meta-analysis. Obstet Gynecol 2020; 135 (5): 1070–1083. doi: 10.1097/AOG.000000000003833.

15. Bartels HC, Postle J, Rogers AC et al. Prophylactic human papillomavirus vaccination to prevent recurrence of cervical intraepithelial neoplasia: a meta-analysis. Int J Gynecolog Cancer 2020; 30 (6): 777–782. doi: 10.1136/ijgc- 2020-001197.

16. Jentschke M, Kampers J, Becker J et al. Prophylactic HPV vaccination after conization: a systematic review and meta-analysis. Vaccine 2020; 38 (41): 6402–6409. doi: 10.1016/ j.vaccine.2020.07.055.

17. Ghelardi A, Parazzini F, Martella F et al. SPERANZA project: HPV vaccination after treatment for CIN2. Gynecol Oncol 2018; 151 (2): 229–234. doi: 10.1016/j.ygyno.2018.08.033.

18. Bogani G, Raspagliesi F, Sopracordevole F et al. Assessing the long-term role of vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): a propensity-score matched comparison. Vaccines (Basel) 2020; 8 (4): 717. doi: 10.3390/vaccines8040717.

19. Bogani G, Lalli L, Sopracordevole F et al. Development of a nomogram predicting the risk of persistence/recurrence of cervical dysplasia. Vaccines (Basel) 2022; 10 (4): 579. doi: 10.3390/vaccines10040579.

20. Gómez de la Rosa AG, Quesada López-Fe A, Vilar Chesa M et al. Efficacy of human papillomavirus vaccination 4 years after conization for high-grade cervical neoplasia. J Low Genit Tract Dis 2021; 25 (4): 287–290. doi: 10.1097/LGT. 0000000000000625.

21. Henere C, Torné A, Llupià A et al. HPV vaccination in women with cervical intraepithelial neoplasia undergoing excisional treatment: insights into unsolved questions. Vaccines (Basel) 2022; 10 (6): 887. doi: 10.3390/vaccines10060 887.

22. Kechagias KS, Kalliala I, Bowden SJ et al. Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis. BMJ 2022; 378: e070135. doi: 10.1136/bmj-2022-070 135.

23. Kjaer SK, Nygård M, Sundström K et al. Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries. EClinicalMedicine 2020; 23: 100401. doi: 10.1016/j.eclinm.2020.100401.

24. Verdoodt F, Dehlendorff C, Kjaer SK. Dose-related effectiveness of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia: a Danish nationwide cohort study. Clin Infect Dis 2020; 70 (4): 608–614. doi: 10.1093/cid/ciz239.

25. Hoffman SR, Le T, Lockhart A et al. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): a systematic review. Int J Cancer 2017; 141 (1): 8–23. doi: 10.1002/ijc.30623.

26. Rob F, Tachezy R, Pichlik T el al. High prevalence of genital HPV infection among long-term monogamous partners of women with cervical dysplasia or genital warts – another reason for HPV vaccination of boys. Dermatol Ther 2017; 30 (1). doi: 10.1111/dth.12435.

27. Ghelardi A, Marrai R, Bogani G et al. Surgical treatment of vulvar HSIL: adjuvant HPV vaccine reduces recurrent disease. Vaccines (Basel) 2021; 9 (2): 83. doi: 10.3390/vaccines9020083.

28. Coskuner ER, Ozkan TA, Karakose A et al. Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV Infection: a randomized study. J Sex Med 2014; 11 (11): 2785–2791. doi: 10.1111/jsm.12670.

29. Swedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis 2012; 54 (7): 891–898. doi: 10.1093/cid/cir1036.

30. Fait T, Dvořák V, Pilka R. Nonavalentní HPV vakcína – nová generace očkování proti HPV. Ceska Gynekol 2015; 80 (6): 397–400.

31. Whitworth HS, Gallagher KE, Howard N et al. Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: a systematic review of evidence from clinical trials. Vaccine 2020; 38 (6): 1302–1314. doi: 10.1016/j.vaccine.2019.12. 017.