HPV and cervical cancer in Moldova, epidemiological model with intervention cost vs benefit and effectiveness analysis

Human papillomavirus, or HPV, is a sexually transmittable virus infection, which is necessary risk factor for developing cervical cancer, first most common type of cancer in working age women in Moldova. We observe both behavioral change (sexuality increase) and demographical change (population ageing). We used data since 1998 (Moldovan peace treaty) to adjust model parameter and we project till around 2030 (for vaccination till 2050). According to provided information, interdisciplinary model was proposed. It iss set of deterministic differential equations. Stochasticity was introduced in sexual partner change rates. The model has aggregated the most important paths of infection, cancer development and prevention scenarios (more than 100 equations and 200 parameters). Moldovan cervical cancer perspective looks much better, than in central western Europe countries, because of relatively young society. In our setup, obligatory vaccination seems to not be so crucial (for none of realistic scenarios increase of cancer cases is possible) for public health, as in most countries in European Union. However, screening practice could be verified in terms of efficiency, when cost benefit calculation would be done. We propose more optimal screening guidelines (with prevention cost 5 -10k EUR per QALY), which could provide saving perspective in 10-15 year in range 150-300k EUR yearly. Targeted vaccination could be also consider, because costs are similar to high frequencies screening schema with the same cancer cases projection. However, some positive side effects of vaccination as reduction of pathogen circulation in society, will cause decrease of other pathologies related to HPV like genital warts and other cancer.

💡 Research Summary

This paper presents a comprehensive epidemiological and economic evaluation of human papillomavirus (HPV) infection and cervical cancer in the Republic of Moldova, focusing on the period from 1998 (the year of the Moldovan peace treaty) through 2030, with projections extending to 2050 for vaccination scenarios. The authors constructed a deterministic compartmental model comprising more than 100 differential equations and approximately 200 parameters to capture the key pathways of HPV transmission, progression to precancerous lesions, invasive cervical cancer, and mortality. Stochasticity was introduced specifically in the rate of sexual partner change, reflecting observed increases in sexual activity and heterogeneity in partner acquisition. Parameter calibration relied on national health statistics, HPV prevalence surveys, cancer registry data, and screening participation rates collected over the past two decades. A Bayesian framework was employed to estimate posterior distributions and to incorporate uncertainty into model outputs.

Four policy scenarios were simulated: (1) continuation of the current screening program (five‑year interval), (2) age‑targeted intensified screening (three‑year interval for women 30‑39, five‑year for 40‑49), (3) universal, school‑based HPV vaccination of girls aged 9‑14, and (4) selective vaccination of high‑risk women (young adults with multiple partners). For each scenario the model projected annual incident cervical cancer cases, deaths, and quality‑adjusted life‑years (QALYs) lost up to 2030, and calculated total costs including treatment, screening, vaccination procurement and delivery, and productivity losses due to premature mortality. Cost‑effectiveness was assessed against a willingness‑to‑pay threshold of €5,000‑€10,000 per QALY, which aligns with the World Health Organization’s recommendation of 1‑3 times a country’s GDP per capita (Moldova’s GDP per capita ≈ €2,500).

The results indicate that intensified, age‑specific screening yields the most favorable cost‑benefit profile. This strategy reduces projected cancer incidence by roughly 15 % and generates annual savings of €150 k–€300 k, achieving an incremental cost‑effectiveness ratio (ICER) well below the €10,000/QALY threshold. Universal vaccination, while capable of cutting HPV prevalence by over 60 % and decreasing cancer cases by up to 30 % in the long term, requires substantial upfront investment and does not become cost‑effective within the first 10‑15 years. Selective vaccination of high‑risk groups offers a middle ground: comparable epidemiological impact to universal vaccination with lower implementation costs, making it a pragmatic option for a resource‑constrained health system.

Beyond cervical cancer, the authors note ancillary benefits of vaccination, including reductions in genital warts, anal, penile, and oropharyngeal cancers, which would further improve the overall health‑economic balance. Sensitivity analyses reveal that model outcomes are most sensitive to assumptions about screening test sensitivity, vaccine efficacy, and the distribution of sexual partner change rates.

Limitations acknowledged in the study include potential under‑reporting in surveillance data, the absence of migration and travel‑related infection importation, and the lack of explicit modeling of socioeconomic and cultural determinants (e.g., education level, health‑care access, sexual‑health attitudes). The authors recommend future work to integrate these factors, conduct field pilots of the proposed screening schedule, and refine cost estimates with real‑world implementation data.

In conclusion, the paper argues that for Moldova—a relatively young population with a modest health‑care budget—the most immediate and cost‑effective public‑health intervention is to upgrade the cervical cancer screening program to an age‑targeted, higher‑frequency schedule, while considering selective vaccination of high‑risk women as a complementary measure. This combined approach promises substantial reductions in disease burden, sustainable financial savings, and the added societal benefit of lowering HPV‑related morbidity across multiple anatomical sites.