Cervical Cytology and Age in HPV-Infected Women in North Macedonia: A Cross-Sectional Study
DOI:
https://doi.org/10.5644/ama2006-124.498Keywords:
HPV, Cervical Cytology, Age, CIN, North MacedoniaAbstract
Objective. HPV infection is a key etiological factor in cervical epithelial alterations and neoplasia. Its prevalence and cytological impact vary with age, co-infections, and screening practices. This study investigated the association between HPV infection, age, and cervical cytological findings in women from North Macedonia.
Materials and Methods. This cross-sectional study included 300 women aged 26–66 years, who were screened over a 13-month period (June 2023–July 2024). The participants were divided into two age groups (26–36 and 37–66 years). All participants underwent Pap testing, HPV screening, and micro- biological evaluation. Ordinal regression analysis was used to examine the associations between age, microbial factors, and HPV positivity.
Results. HPV prevalence was higher in the 37–66 group (12.33%) than in the 26–36 group (6.0%). However, younger age showed a stronger statistical association with HPV positivity (OR=2.10; P<0.1). Cytological abnormalities, particularly LSIL/CIN I, were more prevalent in HPV-positive participants. The use of conventional Pap smears was associated with lower HPV detection (OR=0.16; P<0.05). Co-infection with Candida spp. and atrophic inflammation were inversely associated with HPV positivity.
Conclusion. This study confirmed the association between HPV infection and cytological changes, particularly in younger age groups. These results highlight the importance of age-tailored screening approaches and support the continued use of conventional Pap smears as cost-effective tools. Integrating virological and microbiological assessments may further re- fine cervical cancer prevention strategies, particularly in transitional healthcare systems across the Western Balkans.
References
World Health Organization. Cervical cancer fact sheet. Geneva: WHO; 2021.
Schiffman M, Castle PE. The promise of global cervicalcancer prevention. N Engl J Med. 2005;353(20):2101-4. doi: 10.1056/NEJMp058171.
Muñoz N, Castellsagué X, Berrington de González A, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006;24 Suppl 3:S3/1-10. doi: 10.1016/j.vaccine.2006.05.115.
International Agency for Research on Cancer (IARC). Biological agents. Volume 100B: A review of human carcinogens. Lyon: IARC; 2012.
Shabani V, Reci M, Aliu H, Iseni G, Rexhepi B. Prevalence of human papillomavirus (HPV) genotypes in women from North Macedonia. Op Acc Inter Jour Acad Res UNIVERSES. 2024;3(2):7-20. doi: 10.59710/oaijoaru253205sh.
Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors.
J Low Genit Tract Dis. 2020;24(2):102-31. doi: 10.1097/LGT.0000000000000525. Erratum in: J Low Genit Tract Dis. 2020;24(4):427. doi: 10.1097/LGT.0000000000000563.
Paric A, Tomic K, Alidzanovic L, Fojnica A, Vranic S. HPVRelated Cancers in Bosnia and Herzegovina: A Comprehensive Review. Acta Med Acad. 2024 Dec;53(3):237-273. doi: 10.5644/ama2006-124.458.
Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524-32. doi: 10.1016/S0140-6736(13)62218-7. Epub 2013 Nov 3. Erratum in: Lancet. 2015;386(10002):1446. doi: 10.1016/S0140-6736(15)00411-0.
Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191-e203. doi: 10.1016/S2214-109X(19)30482-6.
Bruni L, Albero G, Serrano B, Mena M, Collado JJ, Gómez D, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human papillomavirus and related diseases in the Republic of North Macedonia: Summary report 10 March 2023 [Internet]. 2023. [cited 2025 Sep 4]. Available from: https://hpvcentre.net/statistics/reports/MKD.pdf.
Franceschi S, Herrero R, Clifford GM, Snijders PJF, Arslan A, Anh PT, et al. Variations in the age-specific curves of human papillomavirus prevalence in women worldwide. Int J Cancer. 2006;119(11):2677-84. doi: 10.1002/ijc.22241.
Nayar R, Wilbur DC, eds. The Bethesda System for reporting cervical cytology: definitions, criteria, and explanatory notes. 3rd ed. Cham, Switzerland: Springer; 2015.
World Health Organization. WHO guidelines for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. Geneva: WHO; 2020.
World Health Organization. Cervical cancer. Geneva: WHO; 2021 [cited 2025 Sep 4]. Available from: https://www.who.int/news-room/fact-sheets/detail/cervicalcancer.
Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401(1):70-9. doi: 10.1016/j.virol.2010.02.002. Epub 2010 Mar 5.
Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890-907. doi: 10.1016/S0140-6736(07)61416-0.
de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.
Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114-9. doi: 10.1001/jama.287.16.2114.
Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011;12(9):880-90. doi: 10.1016/S1470-2045(11)70188-7. Epub 2011 Aug 22.
International Agency for Research on Cancer. Human papillomaviruses. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 100B. Lyon: International Agency for Research on Cancer; 2012.
Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older. Lancet Oncol. 2011;12(9):880-90. doi: 10.1016/S1470-2045(11)70188-7.
Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, et al. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2014;21(5):450-8. doi: 10.1097/GME.0b013e3182a4690b.
Davis M, Feldman MD, Garcia J, Berry J. Diagnostic cytopathology. Philadelphia: Saunders/Elsevier; 2013.
Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, et al. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog. 2020;16(3):e1008376. doi: 10.1371/journal.ppat.1008376.
Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon Det al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197(4):346-55. doi: 10.1016/j.ajog.2007.07.047.
Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006;24 Suppl 1:S1-15. doi: 10.1016/j.vaccine.2005.09.054.
Saslow D, Andrews KS, Manassaram-Baptiste D, Smith RA, Fontham ETH; American Cancer Society Guideline Development Group. Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation. CA Cancer J Clin. 2020;70(4):274-80. doi: 10.3322/caac.21616. Epub 2020 Jul 8.
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