The Impact of Reproductivity and Parity on High-Risk HPV Persistence and Cytological Progression: a Systematic Review and Meta-Analysis
Sadyk Khamitov 1 * ,
Nazira Kamzayeva 1,
Talshyn Ukybassova 2,
Aliya Sailybayeva 2,
Kamila Akzholova 3 More Detail
1 Department of Women's Health, «University Medical Center» Corporate Fund, Astana, Kazakhstan
2 Research Department, «University Medical Center» Corporate Fund, Astana, Kazakhstan
3 Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan, Astana, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, Volume 23, Issue 5, pp. 110-115.
https://doi.org/10.23950/jcmk/19231
OPEN ACCESS
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Author Contributions: Conceptualization, N. K.; methodology, N. K. and T. U.; validation, N. K., T. U., and
A. S.; formal analysis, A. S. and S. K.; investigation, N. K., T. U., and A. S.; resources, N. K.; data curation, A. S. and A. K.; writing original draft preparation, N. K., T. U., and K. A.; writing – review and editing, A. K. and A. S.; project administration,
N. K. The authors have read and agreed to the published version of the manuscript.
Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Artificial Intelligence (AI) Disclosure Statement: The authors declare no AI Tools used for preparation of this work.
ABSTRACT
Persistent infection with a high-risk human papillomavirus is a prerequisite for a cervical malignancy with known factors of smoking, usage of oral contraceptives and quite controversial cofactor of reproductivity history which is evaluated in the context of physiological shift of initial childbirth and the potential dose-response effect of cumulative births.
A systematic review with meta-analysis of five peer reviewed studies from 2016, spanning across Europe and Asia with two main investigations was conducted. Comparisons between nulliparous vs multiparous and between low parity vs high parity were calculated using OR and traditional Cochran’s Q test and I2 statistic.
Analysis between nulliparous vs multiparous cohorts reported uniform, negligible baseline risk (OR 1.06 [0.86-1.31]) with low heterogeneity I2 =13.36%, p=0.283. Conversely, analysis between low and high parity revealed a significant compounding risk associated with high parity with pooled OR 2.27 [1.84-2.79], although the heterogeneity was substantial (I2 =69.12%, p=0.021).
The physiological experience of childbirth itself doesn’t significantly alter the risk of HR-HPV persistence but the high parity may serve as context-dependent predictor of cytological progression and cervical carcinoma, likely explained by hormonal shifts and socioeconomic factors.
CITATION
Khamitov S, Kamzayeva N, Ukybassova T, Sailybayeva A, Akzholova K. The Impact of Reproductivity and Parity on High-Risk HPV Persistence and Cytological Progression: a Systematic Review and Meta-Analysis. J CLIN MED KAZ. 2026;23(5):110-5.
https://doi.org/10.23950/jcmk/19231
REFERENCES
- Stensen S, Kjaer SK, Jensen SM, Frederiksen K, Junge J, Iftner T, Munk C. Factors associated with type-specific persistence of high-risk human papillomavirus infection: A population-based study. International Journal of Cancer. 2016; 138 (2): 361-367. https://doi.org/10.1002/ijc.29719.
- Senapati R, Nayak B, Kar SK, Dwibedi B. HPV Genotypes distribution in Indian women with and without cervical carcinoma: Implication for HPV vaccination program in Odisha, Eastern India. BMC Infectious Diseases. 2017; 17 (1): 30. https://doi.org/10.1186/s12879-016-2136-4
- Shrivastava G, Faras V, Jawarkar A, Patadia H. Prevalence, Genotype Distribution, and Risk Factor Analysis of High-Risk Human Papillomavirus Among Reproductive-Aged Women in Central Gujarat: A Community-Based Screening Study. Research Square (Preprint). 2026. https://doi.org/10.21203/rs.3.rs-8324888/v1.
- Pankaj S, Rani J, Kumari P, Abhilashi K, Choudhary V, Kumari S, Shahi SK, Jee B. Prevalence, risk factors and genotype distribution of human papillomavirus infection among women with and without invasive cervical cancer: Findings from a hospital-based study in Bihar, India. The National Medical Journal of India. 2024; 37 (1): 13-17. https://doi.org/10.25259/NMJI_634_21.
- Rizzuto I, Nalam M, Jiang J, Linder A, Rufford B. Risk factors for HPV persistence and cytology anomalies at follow-up after treatment for cervical dysplasia. International journal of Gynecology and Obstetrics. 2018; 141 (2): 218-224. https://doi.org/10.1002/ijgo.12431.
- Imankulova B.Zh., Kamzayeva N.K., Galym M.S., Makhambetova S.B., Ibrayeva Zh.N., Tleuberdieva Z.T., Baitas Y.B., Ukybassova T.M. The role of socio-demographic factors in HPV infection. Medicine and ecology. 2025;(3):55-65. https://doi.org/10.59598/ME-2305-6053-2025-116-3-55-65
- Sharifian K, Shoja Z, Jalilvand S. The interplay between human papillomavirus and vaginal microbiota in cervical cancer development. Virology Journal. 2023; 20: 73. https://doi.org/10.1186/s12985-023-02037-8
- Zhang W, Ge Y, Yao L, Yan Q, Wei J, Yin Y, Liu B. Changes of Microbiome in Human Papillomavirus Infection and Cervical Cancer: A Systematic Review and Meta-Analysis. Cancer Reports. 2025; 8 (6): e70246. https://doi.org/10.1002/cnr2.70246
- Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome. 2016; 4 (1): 58. https://doi.org/10.1186/s40168-016-0203-0
- Sharipova IP, Musabaev EI, Sadirova SS, Suyarkulova DT, Tashev SE, Akhmedova SK, Turabova NR, Sharapov SM, Kasimova RI, Rakhimov RA, Yuldashova GT, Lee K, Chun G, Kim H. Prevalence of high-risk human papillomavirus genotypes among women in Uzbekistan, 2021-2023. J Gynecol Oncol. 2025; 36 (1): e7. https://doi.org/10.3802/jgo.2025.36.e7
- Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, Bray F. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health. 2020; 8 (2): e191–e203. https://doi.org/10.1016/S2214-109X(19)30482-6
- Teame H, Gebremariam L, Kahsay T, Berhe K, Gebreheat G, Gebremariam G. Factors affecting utilization of cervical cancer screening services among women attending public hospitals in Tigray region, Ethiopia, 2018; case control study. PLoS One. 2019; 14 (3): e0213546. https://doi.org/10.1371/journal.pone.0213546
- Moreno V, Bosch FX, Muñoz N, Meijer CJ, Shah KV, Walboomers JM, Herrero R, Franceschi S. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case–con-trol study. Lancet (London, England). 2002; 359 (9312): 1085–1092. https://doi.org/10.1016/S0140-6736(02)08150-3
- Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia. Research in Microbiology, 2016; 167 (1): 26–33 https://doi.org/10.1038/srep16865
- Kim Y, Ukybassova T, Bapayeva G, Kongrtay K, Kamzayeva N, Imankulova B. The role of the cervicovaginal microbiome and local immunity in human papillomavirus persistence and precancerous cervical changes. Vestnik Khirurgii Kazakhstana [Surgery Bulletin of Kazakhstan]. 2025; 82 (1): 59–71. https://doi.org/10.35805/BSK2025I008
- Balmagambetova SK, Zholdybayeva EV, Zavalennaya OV, Amanzholkyzy A, Kononets VI, Zharmakhanova GM, Mussin NM, Zhamilyeva LM, Kereyeva NM. High-risk human papillomaviruses L1 gene isolates identified in Western Kazakhstan. J Clin Med Kaz. 2024; 21 (1): 26-34. https://doi.org/10.23950/jcmk/14274
- Çakir AT, Özten MA. Serum vitamin D levels in high-risk HPV infected patients, is there any relation? J Clin Med Kaz. 2022; 19 (3): 35-39. https://doi.org/10.23950/jcmk/12113
- Tekalegn Y, Sahiledengle B, Woldeyohannes D, Atlaw D, Degno S, Desta F, Bekele K, Aseffa T, Gezahegn H, Kene C. High parity is associated with increased risk of cervical cancer: Systematic review and meta-analysis of case-control studies. Womens Health (Lond). 2022 doi: https://doi.org/10.1177/17455065221075904 .
- Kydyrbayeva EA, Iztleuov YM, Azamatova IA, Iztleuova GM, Sultangereyev YB, Abenova NA. Association of Vaginal Microbiota Composition with Human Papillomavirus Persistence in Cervical Dysplasia and Cervical Cancer: a Systematic Review and Meta-Analysis. J Clin Med Kaz. 2026;23(3):92-102. https://doi.org/10.23950/jcmk/18531