Effectiveness of vaccination in the treatment of early lesions of the cervix in women with infertility





infertility, early cervical lesions, interleukin-6, interleukin-8, secretory inhibitor of leukocyte proteinase, lactoferrin, vaccination, human papilloma virus


Infertility is a common pathology that has not only medical, but powerful social and economic consequences.

The aim of the study - to investigate the impact of human papillomavirus (HPV) vaccination on indicators of local cervical immunity in women with infertility.

Materials and methods. 133 patients with infertility were examined, in whom abnormal cytological findings and DNA of one or more HPV strains were detected during the initial examination. Among them, 28 women had infertility of endocrine origin (the Group I), 52 women had tubo-peritoneal origin (the Group II) and 53 patients had male factors of infertility (the Group III). After treatment, which included the elimination of pathogens and excision of the affected epithelium, the patients were divided into subgroups A and B. Subgroup IA included 13 patients, subgroup IV included 13 patients, IIA included 28 patients, IIV included 24 patients, IIIA included 27 patients, IIIB included 26 patients. Patients of subgroup A were offered vaccination with a 2-component vaccine against HPV, patients of subgroup B were limited to traditional therapy. In the control group were 37 healthy women with normal cytological results. The concentration of interleukin 8 (IL-8), IL-6, lactoferrin (L) and secretory leukocyte proteinase inhibitor (SLPI) was assessed before the start of treatment, 3 and 6 months after treatment.

Results. In all patients with infertility and early cervical lesions (ECL), a three-fold increased concentration of IL-8, IL-6, as well as SLPI and L, which has a direct impact on fertility disorders, was found. Against the background of traditional therapy, a decrease in IL-6 was found in all patients after 6 months, and in patients with infertility of endocrine origin was found in the concentration of L. Additional vaccination allows to achieve a decrease in the cervical content of all inflammatory markers within 6 months, which is important for the further restoration of reproductive function.

Conclusions. Increased cervical content of pro-inflammatory markers: IL-6, IL-8, SLPI and L, which are important in the pathogenesis of reproductive function disorders, were found in patients with ECL against the background of infertility. Against the background of anti-inflammatory therapy and surgical treatment for 6 months, there is a slight decrease in the cervical concentration of IL-8 and SLPI. Vaccination with a bivalent vaccine against HPV in combination with anti-inflammatory therapy and surgical treatment in women with ECL and infertility led to the normalization of the concentration of pro-inflammatory markers in cervical mucus.

The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the women was obtained for the research.

No conflict of interests was declared by the authors.


Amouyal M, Boucekine O, Paulmyer-Lacroix A et al. (2020). No specific adverse pregnancy outcome in singleton pregnancies after assisted reproductive technology (ART) for unexplained infertility. Journal of Gynecology Obstetrics and Huатпman Reproduction. 49 (1): 101623. https://doi.org/10.1016/j.jogoh.2019.08.006; PMid:31446168

Deshpande P, Gupta A. (2019). Causes and Prevalence of Factors Causing Infertility in a Public Health Facility. J Hum Reprod Sci. 12(4): 287-293. https://doi.org/10.4103/jhrs.JHRS_140_18; PMid:32038077 PMCid:PMC6937760

Ghelardi A, Parazzini F, MartellaF et al. (2018). HPV vaccination after treatment for CIN2. Gynecol Oncol. 151: 229-234. https://doi.org/10.1016/j.ygyno.2018.08.033; PMid:30197061

Harro C, Pang Y, Roden R et al. (2001). Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine. J Natl Cancer Inst. 93: 284-292. https://doi.org/10.1093/jnci/93.4.284; PMid:11181775

Incognito G, Di Guardo F, Gulino F et al. (2023). Interleukin-6 as A Useful Predictor of Endometriosis-Associated Infertility: A Systematic Review. International Journal of Fertility and Sterility. 17(4): 226-230. doi: 10.22074/ijfs.2023.557683.1329.

Jenabi M, Khodarahmi P, Tafvizi F et al. (2022). Evaluation of expression CXCL8 chemokine and its relationship with oocyte maturation and embryo quality in the intracytoplasmic sperm injection method. Mol Biol Rep. 49: 8413-8427. https://doi.org/10.1007/s11033-022-07660-2; PMid:35781602

Jia L, Li F, Shao M et al. (2018). IL-8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells. Oncol Lett. 15(1): 1350-1356. https://doi.org/10.3892/ol.2017.7391

Kechagias K, Kalliala I, Bowden S. (2022). 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. 378: e070135. https://doi.org/10.1136/bmj-2022-070135; PMid:35922074 PMCid:PMC9347010

Kurtay S, Ali KY, Hussein A. (2022). Frequency of cervical premalignant lesions in the gynecologic patients of a tertiary hospital in Mogadishu, Somalia. BMC Women's Health. 22(I1): 501. https://doi.org/10.1186/s12905-022-02106-0; PMid:36476212 PMCid:PMC9727848

Lehoux M, D'Abramo C, Archambault J. (2009). Molecular mechanisms of human papillomavirus-induced carcinogenesis. Public Health Genomics. 12(5-6): 268-280. https://doi.org/10.1159/000214918; PMid:19684440 PMCid:PMC4654617

Madendag I, Sahin M, Madendag Y, Sahin E, Karakukcu C. (2020). Evaluation of the levels of secretory leukocyte protease inhibitor in the cervical mucus of women with unexplained infertility. J. Obstet. Gynaecol. Res. 46: 1128-1132. https://doi.org/10.1111/jog.14299; PMid:32410306

Naik S, Kumar V, Joshi R et al. (2016). HPV inflammation mediate IL-6 through STAT3 signaling pathway in different grades of cervical cancer. Cancer Res Mol Med. 3: 103-105.

Paavonen J, Naud P, Salmerón J et al. (2009). Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 374: 301-314. https://doi.org/10.1016/S0140-6736(09)61248-4; PMid:19586656

Sand F, Kjaer S, Frederiksen K, Dehlendorff C. (2020). Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status. Int J Cancer. 147: 641-647. https://doi.org/10.1002/ijc.32752; PMid:31648368

Sereda K. (2023). Patolohiia tservikalnoho epiteliiu u zhinok z riznymy formamy bezplidnosti. Reproduktyvne zdorov'ia zhinky. 67: 44-49. https://doi.org/10.30841/2708-8731.4.2023.285764

Sereda KV. (2023). State of local cervical immunity in women with infertility. Ukrainian Journal Health of Woman. 5(168): 28-33. https://doi.org/10.15574/HW.2023.168.28

Singh A, Pandey K, Arya S, Ahmad A, Khatoon F. (2020). Role Of Interleukin-8 In Predicting Endometriosis In Patients With Chronic Pelvic Pain & Infertility. Era J. Med. Res. 7(2): 1-5. https://doi.org/10.24041/ejmr2020.30

Stanley M. (2010). HPV - immune response to infection and vaccination. Infect Agent Cancer. 20; 5: 19. https://doi.org/10.1186/1750-9378-5-19; PMid:20961432 PMCid:PMC3161350

Sung H, Ferlay J, Siegel R et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71: 209-249. https://doi.org/10.3322/caac.21660; PMid:33538338

Zacharis K, Messini C, Anifandis G. (2018). Human Papilloma Virus (HPV) and Fertilization: A Mini Review. Medicina (Kaunas). 27; 54(4): 50. https://doi.org/10.3390/medicina54040050; PMid:30344281 PMCid:PMC6174353