Recurrence Factors in Cervical Precancerous Lesions

A Narrative Exploration

Authors

  • Fitriyadi Kusuma Divisi Ginekologi Onkologi, Departemen Obstetri dan Ginekologi, Fakultas Kedokteran, Universitas Indonesia-Rumah Sakit Cipto Mangunkusumo
  • Geraldus Sigap Gung Binathara Faculty of Medicine, Universitas Indonesia
  • Kemal Akbar Suryoadji Faculty of Medicine, Universitas Indonesia
  • Tsaniya Meidini Tahsya Hermawan Faculty of Medicine, Universitas Indonesia
  • Vira Nur Arifa Faculty of Medicine, Universitas Indonesia
  • Marshaly Safira Masrie Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo General Hospital

DOI:

https://doi.org/10.53088/griyawidya.v5i2.2287

Keywords:

Cervical lesion, Conization, HPV infection, Recurrence, Vaccination

Abstract

Background: Recurrent cervical pre-cancerous lesions remain a major clinical challenge in preventing progression to invasive cancer and achieving long-term remission. Persistent infection with high-risk human papillomavirus (HPV), particularly subtype 16, is strongly associated with recurrence, especially in women under 40 years of age.

Method: This narrative review analyzed recent literature focusing on the main determinants of recurrence after treatment of cervical pre-cancerous lesions, including viral, surgical, and immunological factors.

Result: The findings showed that incomplete surgical excision significantly increased the risk of recurrence. The type of surgical procedure also influenced outcomes, with cold knife and laser conization associated with lower recurrence rates than LLETZ. Post-treatment HPV vaccination was found to reduce recurrence by enhancing immunity against re-infection.

Implication: These findings highlight the importance of individualized treatment selection, complete lesion excision, and the use of HPV vaccination as part of a comprehensive strategy to minimize recurrence and improve long-term outcomes.
Novelty: This review provides an integrated overview of viral, surgical, and immunological factors influencing cervical lesion recurrence, emphasizing the importance of combining optimal surgical technique with preventive immunization.

References

Arbyn, M., Redman, C. W. E., Verdoodt, F., Kyrgiou, M., Tzafetas, M., Ghaem-Maghami, S., … Moss, E. L. (2017). Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. The Lancet Oncology, 18(12), 1665–1679. doi:10.1016/S1470-2045(17)30700-3

Ashique, S., Hussain, A., Fatima, N., & Altamimi, M. A. (2023). HPV pathogenesis, various types of vaccines, safety concern, prophylactic and therapeutic applications to control cervical cancer, and future perspective. VirusDisease, 34(2), 172–190. doi:10.1007/s13337-023-00824-z

Burmeister, C. A., Khan, S. F., Schäfer, G., Mbatani, N., Adams, T., Moodley, J., & Prince, S. (2022). Cervical cancer therapies: Current challenges and future perspectives. Tumour Virus Research, 13, 200238. doi:10.1016/j.tvr.2022.200238

Byun, J. M. (2018). Persistent HPV-16 infection leads to recurrence of high-grade cervical intraepithelial neoplasia - PubMed. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30572469/

Depuydt, C. E., Thys, S., Beert, J., Jonckheere, J., Salembier, G., & Bogers, J. J. (2016). Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer. International Journal of Cancer, 139(9), 2021–2032. doi:10.1002/ijc.30238

Di Donato, V., Caruso, G., Bogani, G., Cavallari, E. N., Palaia, G., Perniola, G., … Palaia, I. (2022, February 1). HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. Vaccines. MDPI. doi:10.3390/vaccines10020239

Galagali, P. M., Kinikar, A. A., & Kumar, V. S. (2022). Vaccine Hesitancy: Obstacles and Challenges. Current Pediatrics Reports, 10(4), 241–248. doi:10.1007/s40124-022-00278-9

Gertig, D. M., Brotherton, J. M. L., Budd, A. C., Drennan, K., Chappell, G., & Saville, A. M. (2013). Impact of a population-based HPV vaccination program on cervical abnormalities: A data linkage study. BMC Medicine, 11(1). doi:10.1186/1741-7015-11-227

Giannini, A., Di Donato, V., Sopracordevole, F., Ciavattini, A., Ghelardi, A., Vizza, E., … Bogani, G. (2023). Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization. Vaccines, 11(3), 698. doi:10.3390/vaccines11030698

Han, L., & Zhang, B. (2023, December 1). Can prophylactic HPV vaccination reduce the recurrence of cervical lesions after surgery? Review and prospect. Infectious Agents and Cancer. BioMed Central Ltd. doi:10.1186/s13027-023-00547-2

Hariri, S., Johnson, M. L., Bennett, N. M., Bauer, H. M., Park, I. U., Schafer, S., … Markowitz, L. E. (2015). Population-based trends in high-grade cervical lesions in the early human papillomavirus vaccine era in the United States. Cancer, 121(16), 2775–2781. doi:10.1002/cncr.29266

Hewavisenti, R. V., Arena, J., Ahlenstiel, C. L., & Sasson, S. C. (2023). Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk. Frontiers in Immunology, 14. doi:10.3389/FIMMU.2023.1112513

Hilal, Z., Rezniczek, G. A., Alici, F., Kumpernatz, A., Dogan, A., Alieva, L., & Tempfer, C. B. (2018). Loop electrosurgical excision procedure with or without intraoperative colposcopy: a randomized trial. American Journal of Obstetrics and Gynecology, 219(4), 377.e1-377.e7. doi:10.1016/j.ajog.2018.07.023

Hoffman, S. R., Le, T., Lockhart, A., Sanusi, A., Dal Santo, L., Davis, M., … Smith, J. S. (2017, July 1). Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review. International Journal of Cancer. Wiley-Liss Inc. doi:10.1002/ijc.30623

Jacobson, R. M., St. Sauver, J. L., Griffin, J. M., MacLaughlin, K. L., & Finney Rutten, L. J. (2020). How health care providers should address vaccine hesitancy in the clinical setting: Evidence for presumptive language in making a strong recommendation. Human Vaccines & Immunotherapeutics, 16(9), 2131–2135. doi:10.1080/21645515.2020.1735226

Jiang, Y.-M., Chen, C.-X., & Li, L. (2016). Meta-analysis of cold-knife conization versus loop electrosurgical excision procedure for cervical intraepithelial neoplasia. OncoTargets and Therapy, 9, 3907–3915. doi:10.2147/OTT.S108832

Kliemann, L. M., Silva, M., Reinheimer, M., Rivoire, W. A., Capp, E., & dos Reis, R. (2012). Minimal cold knife conization height for high-grade cervical squamous intraepithelial lesion treatment. European Journal of Obstetrics & Gynecology and Reproductive Biology, 165(2), 342–346. doi:10.1016/j.ejogrb.2012.08.016

Koshiol, J., Lindsay, L., Pimenta, J. M., Poole, C., Jenkins, D., & Smith, J. S. (2008). Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. American Journal of Epidemiology, 168(2), 123–137. doi:10.1093/AJE/KWN036

Kreimer, A. R., Schiffman, M., Herrero, R., Hildesheim, A., González, P., Burk, R. D., … Rodríguez, A. C. (2012). Long-term risk of recurrent cervical HPV infection and precancer and cancer following excisional treatment. International Journal of Cancer. Journal International Du Cancer, 131(1), 211–218. doi:10.1002/ijc.26349

Lacey, C. J. N. (2023). Unresolved issues in the management of human papillomavirus-associated mucosal high-grade pre-cancers. Tumour Virus Research, 15, 200250. doi:10.1016/j.tvr.2022.200250

Li, Z., Barron, S., Hong, W., Karunamurthy, A., & Zhao, C. (2013). Surveillance for recurrent cancers and vaginal epithelial lesions in patients with invasive cervical cancer after hysterectomy: are vaginal cytology and high-risk human papillomavirus testing useful? American Journal of Clinical Pathology, 140(5), 708–714. doi:10.1309/AJCPH4AFSZHU8EKK

Movahed, F., Darzi, S., Mahdavi, P., Salih Mahdi, M., Qutaiba B. Allela, O., Naji Sameer, H., … Gholizadeh, O. (2024). The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV). Virology Journal, 21(1), 124. doi:10.1186/s12985-024-02397-9

Pathak, P., Pajai, S., & Kesharwani, H. (2024). A Review on the Use of the HPV Vaccine in the Prevention of Cervical Cancer. Cureus, 14(9), e28710. doi:10.7759/cureus.28710

Pinto, L. A., Dillner, J., Beddows, S., & Unger, E. R. (2018). Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development. Vaccine, 36(32Part A), 4792–4799. doi:10.1016/j.vaccine.2017.11.089

Scherer-Quenzer, A. C., Findeis, J., Herbert, S. L., Yokendren, N., Reinhold, A. K., Schlaiss, T., … Kiesel, M. (2024). The value of endocervical curettage during large loop excision of the transformation zone in combination with endocervical surgical margin in predicting persistent/recurrent dysplasia of the uterine cervix: a retrospective study. BMC Women’s Health, 24(1). doi:10.1186/S12905-024-03291-W

Setiawan, D., Kotsopoulos, N., Wilschut, J. C., Postma, M. J., & Connolly, M. P. (2016). Assessment of the broader economic consequences of HPV prevention from a government-perspective: A fiscal analytic approach. PLoS ONE, 11(8). doi:10.1371/journal.pone.0160707

Simms, K. T., Keane, A., Nguyen, D. T. N., Caruana, M., Hall, M. T., Lui, G., … Canfell, K. (2023). Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population. Nature Medicine, 29(12), 3050–3058. doi:10.1038/s41591-023-02600-4

Stern, P. L., & Roden, R. B. S. (2019). Opportunities to improve immune-based prevention of HPV-associated cancers. Papillomavirus Research, 7, 150–153. doi:10.1016/j.pvr.2019.04.010

Vargas, S., Valente, M. P., Almeida, M. M. de, Neves, J., & Calhaz-Jorge, C. (2019). Isolated Non-16/18 High-Risk Human Papillomavirus Cervical Infection: Re-Evaluation After One Year. Acta Medica Portuguesa, 32(9), 588–592. doi:10.20344/AMP.10183

Wang, R., Pan, W., Jin, L., Huang, W., Li, Y., Wu, D., … Liao, S. (2020). Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Letters, 471, 88–102. doi:10.1016/J.CANLET.2019.11.039

Wenpeng Wang, Jusheng An, Yan Song, Minjie Wang, Manni Huang, Lingying Wu, (2017) Distribution and attribution of high-risk human papillomavirus genotypes in cervical precancerous lesions in China - https://journals.sagepub.com/doi/10.1177/1010428317707373

Williams, V. M., Filippova, M., Soto, U., & Duerksen-Hughes, P. J. (2011). HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virology, 6(1), 45–57. doi:10.2217/fvl.10.73

Yokomine, M., Matsueda, S., Kawano, K., Sasada, T., Fukui, A., Yamashita, T., … Ushijima, K. (2017). Enhancement of humoral and cell mediated immune response to HPV16 L1-derived peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like particle vaccine in healthy females. Experimental and Therapeutic Medicine, 13(4), 1500–1505. doi:10.3892/etm.2017.4150

Zeng, F., Guo, P., Xia, M., & He, M. (2024). Total hysterectomy versus radical hysterectomy in neuroendocrine cervical cancer: a SEER-database analysis. Journal of Cancer Research and Clinical Oncology, 150(5). doi:10.1007/S00432-024-05773-8

Zhang, H., Zhang, T., You, Z., & Zhang, Y. (2015). Positive Surgical Margin, HPV Persistence, and Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization. PLoS ONE, 10(12), e0142868. doi:10.1371/journal.pone.0142868

Zhang, L., Shi, X., Zhang, Q., Mao, Z., Shi, X., Zhou, J., … Lu, W. (2022). HPV-16 E7-Specific Cellular Immune Response in Women With Cervical Intraepithelial Lesion Contributes to Viral Clearance: A Cross-Sectional and Longitudinal Clinical Study. Frontiers in Immunology, 12. doi:10.3389/FIMMU.2021.768144

Zhou, C., Tuong, Z. K., & Frazer, I. H. (2019). Papillomavirus Immune Evasion Strategies Target the Infected Cell and the Local Immune System. Frontiers in Oncology, 9, 682. doi:10.3389/fonc.2019.00682

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Published

2026-04-29

How to Cite

Kusuma, F., Gung Binathara, G. S., Suryoadji, K. A., Tahsya Hermawan, T. M., Arifa, V. N., & Masrie, M. S. (2026). Recurrence Factors in Cervical Precancerous Lesions: A Narrative Exploration. Griya Widya: Journal of Sexual and Reproductive Health, 5(2), 59–69. https://doi.org/10.53088/griyawidya.v5i2.2287