Determinants of HPV vaccine hesitancy and acceptance: a comparative cross-sectional analysis of Ukrainian and international cohorts

Received 7.08.2026
Accepted 18.08.2026

DOI: 10.32471/clinicaloncology.2663-466X.36544

INTRODUCTION

HPV is the primary etiological agent of cervical cancer, driving oncogenesis through E6 and E7 oncoproteins, which inactivate the tumor suppressors p53 and Rb [1]. The current two-pronged strategy for disease control combines primary prevention through vaccination — most effective before sexual debut — with regular screening, which remains mandatory even for vaccinated individuals [2]. HIV-positive patients require particular attention due to substantially higher risks of viral persistence and disease progression [1].

Globally, the burden of cancer attributable to infections, including HPV, is substantial. C. de Martel et al. reported that in 2018, infections caused approximately 2.2 million new cancer cases worldwide, with HPV accounting for a significant proportion [3]. For patients aged 15–26 years, a three-dose catch-up vaccination schedule is recommended, which does not require prior screening but also does not obviate future screening [4]. Although lacking therapeutic activity against established infections, 9-valent vaccines provide effective protection against other oncogenic HPV types [4].

Beyond cervical cancer, accumulating evidence implicates HPV in breast cancer — the most common female malignancy worldwide. A meta-analysis by N.A. Salman et al. reported that high-risk HPV DNA is detected in breast cancer tissue with an odds ratio of 4.02 (95% CI 2.45–6.58) compared to benign breast tissue [5]. N. Khodabandehlou et al. provided a comprehensive review of HPV in breast cancer, highlighting the role of E6 and E7 oncoproteins in breast carcinogenesis [6]. J.S. Lawson and W.K. Glenn presented evidence for a causal role of HPV in breast cancer, suggesting that the virus may reach breast tissue via lymphohematogenous spread from anogenital sites [7].

Beyond prophylaxis, postsurgical vaccination reduces cervical intraepithelial neoplasia (CIN) II–III recurrence from 5.3 to 3.1% by preventing reinfection of healthy cells [1]. The World Health Organization (WHO) validation of single-dose schedules and recognition of vaccination as an effective means of preventing recurrence after surgery represent important breakthroughs, although the emergence of HPV type 35 — not covered by current vaccines — creates a critical gap [8]. Modelling studies by K. Canfell et al. demonstrated that achieving WHO cervical cancer elimination targets would prevent millions of deaths, particularly in low- and middle-income countries [9].

Given the high HPV prevalence among men (over 50%) and the absence of systematic screening, gender-neutral vaccination has become a fundamental population-level strategy [10]. The strategic shift to single-dose schedules and thermostable vaccines, combined with active screening, makes cervical cancer elimination a realistic clinical goal [11]. HPV vaccination also reduces cervical cancer risk in vaccinated populations, as demonstrated in long-term follow-up studies [12].

Timing of administration is fundamental to the vaccine’s effectiveness. When children get the shot from ages 9 to 14, they can get protection from 74 to 93% [13]. But postponing the vaccination has a major impact on this defense. For instance, when the series started at age 17 or 18, the protective effect against invasive cancer drops from 88 to 53%. The reduction is even greater in preventing precancerous lesions; after age 20, for example, if you administer the vaccine your protection from cancer falls below 25% [13]. Finally, early immunization offers about four times more protection in theory. Moreover, beginning the process at age 9 actually accelerates the completion rate of courses up to as much as 97.5%, which is an improvement from the 78% completion rate at ages 11 or 12 [14]. However, despite this strong immunogenicity and high safety profile on the part of the vaccines, the continuing prevalence of misinformation drives vaccine hesitancy [15], thus creating a significant barrier to the global elimination.

H.J. Larson et al. described the global «vaccine-hesitant moment», emphasising that trust in vaccines is fragile and context-dependent [15]. Major barriers include needle sensitivity and concerns about reproductive safety, which in certain parent samples reach 80% [16]. The decisive factor in increasing coverage is a direct doctor recommendation [16, 17]. The WHO SAGE Vaccine Hesitancy Scale provides a validated instrument to measure these barriers [18].

Men are essential vectors: in 87% of couples, complete viral strain concordance drives persistent reinfections in female partners. Gender-neutral vaccination can eliminate HPV 16 when 75% of adolescents of both sexes are covered, providing herd immunity [19]. A. Krawczyk et al. showed that vaccination intention and uptake among college women were strongly influenced by physician recommendations and perceived risk [20]. Religious beliefs, lack of trust, and myths about infertility or early sexual activity contribute to low vaccine acceptance in developing countries (46.5%) [21]. Vaccination rates between regions vary from 30 to 54%, and education plays a large role: girls with high knowledge are 3.89 times more likely to accept vaccination [21].

Low- and middle-income countries account for 90% of global cervical cancer mortality, with adolescent vaccination coverage as low as 3% [22]. Fear of infertility is shared by over 42% of parents, transforming reproductive health misinformation into a key threat to national immunisation strategies [22]. The 9-valent vaccine prevents 92% of HPV-associated cancers, and the presumptive approach — presenting vaccination as a default procedure — changes the decision of 70% of initially hesitant parents [23].

In solid organ transplant recipients, the risk of HPV-associated anogenital malignancies is significantly higher due to immunosuppression, yet evidence-based screening protocols are lacking [24]. Comprehensive insights into HPV pathophysiology, screening, and vaccination strategies emphasise the need for integrated approaches [23].

Study aim. To analyse determinants of HPV vaccine hesitancy and acceptability through comparison of levels of awareness, perceived barriers and willingness to vaccinate across both Ukrainian and international cross-sectional populations.

MATERIALS AND METHODS

Ethical considerations. The study was conducted in accordance with the Declaration of Helsinki. Participation was entirely voluntary and anonymous. Digital informed consent was obtained from all participants on the landing page of the survey; respondents had to explicitly click «I agree to participate» before accessing the questionnaire questions. No personally identifiable medical data or IP addresses were stored in the final dataset.

Study design and setting. We conducted a comparative, cross-sectional online survey between January and February 2026. The study aimed to assess and compare the determinants of HPV vaccine hesitancy among women residing in Ukraine and an international cohort comprising respondents from 12 other countries. The research was reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies.

Participants and recruitment procedure. We utilized a convenience sampling method with a snowball approach to recruit participants. The survey link was distributed through digital channels, primarily social media platforms (Facebook, Instagram), student network groups, and professional academic forums associated with Uzhhorod National University. The inclusion criteria for the study were: 1) female gender; 2) age 18 years and older; and 3) the ability to read and understand either Ukrainian or English. We excluded incomplete questionnaires or responses submitted by individuals identifying as male or under the age of 18. To prevent duplicate submissions, the survey platform was configured to limit responses to one per IP address / user account. A post hoc power analysis for χ² tests (α=0.05; effect size w=0.30) indicated that the total sample (n=365) provides 87% power to detect moderate differences.

Survey instrument development and measures. Data were collected using a structured, self-administered questionnaire. The survey was developed by the research team based on a review of current literature and the WHO SAGE guidelines regarding vaccine hesitancy. The instrument was made available in two languages: Ukrainian and English. To ensure face validity and clarity, a pilot test was conducted with 15 independent respondents before the main launch; their feedback was used to refine the wording, though pilot data were not included in the final analysis.

The final questionnaire consisted of four primary sections: sociodemographic characteristics: age group, educational level, and country of residence.

Baseline Knowledge and Screening: awareness of HPV, knowledge of gender-neutral vaccination, and history of cervical cancer screening (e.g., Pap smear testing).

Information Sources: primary channels used to obtain medical information (e.g., physicians, social media, scientific articles).

Barriers and Willingness: subjective obstacles to vaccination (e.g., fear of side effects, lack of doctor’s recommendation, financial cost) and the overall willingness to vaccinate oneself or one’s children.

The primary outcome variable (dependent variable) was defined as the «willingness to vaccinate», categorized dichotomously (Yes / No). Subjective barriers and demographic factors served as the independent predictor variables.

Sample Size Justification. While this was an exploratory convenience sample, a post-hoc power analysis confirmed the adequacy of our sample size. With a total of 365 valid responses (293 Ukrainian, 72 international), the study maintains a 95% confidence level with a margin of error of approximately 5%, assuming a standard 50% response distribution for vaccine acceptance.

Statistical Analysis. All statistical analyses were performed using (the jamovi software version 2.4). Descriptive statistics were used to summarize categorical variables as frequencies and percentages. To compare differences in awareness, barriers, and willingness between the Ukrainian and international cohorts, we utilized Pearson’s Chi-square (χ²) test. To identify the strongest independent predictors of vaccine refusal, variables that showed potential significance in the univariate analysis were entered into a multivariable binary logistic regression model. The results of the regression are presented as OR with corresponding 95% CI. A p-value of <0.05 was considered statistically significant for all tests.

Data availability. The data associated with the paper are not publicly available due to privacy restrictions but are available from the corresponding author on reasonable request.

RESULTS

The Ukrainian group was older and more likely to have children, while the international group predominantly consisted of young, urban, highly educated women without children (Table 1).

The international sample is significantly younger, more urban, more highly educated, less often married, and less likely to have children compared to the Ukrainian sample. All differences are statistically significant at p <0.05. These differences should be considered when interpreting group comparisons in subsequent tables.

Ukrainian women reported significantly higher HPV awareness and better knowledge of gender-neutral vaccination (Table 2).

Ukrainian women have significantly higher HPV awareness and better knowledge that vaccination is recommended for boys as well. International respondents rely on social media as their primary information source 2.4 times more often than Ukrainians (26.4 vs 10.9%; p=0.002), which may increase exposure to vaccine misinformation.

The distribution of self-reported main barriers to HPV vaccination of a child, the proportion of women who have not undergone cervical screening (Pap smear / HPV test) in the last 3 years, and the proportion willing to vaccinate their child if the vaccine were free and available at their local clinic (Table 3).

Fear of side effects is the dominant barrier in Ukraine (39.2%), while international respondents are twice as likely to report having no barriers at all (36.1 vs 17.7%, p <0.001). Screening uptake is critically low in both groups (>65% have not been screened in 3 years). Willingness to vaccinate if free is high (>75%) and does not differ significantly between groups (p=0.26), suggesting that removing financial barriers could be an effective policy lever in both contexts.

Table 4 displays the results of binary logistic regression with willingness to vaccinate child (yes / no) as the dependent variable. The reference category for each predictor is indicated in parentheses. OR > 1 indicate a higher odds of vaccine hesitancy / NOT being willing to vaccinate (compared to the reference category), while OR <1 indicates lower odds of hesitancy.

Table 4 presents the results of the binary logistic regression analysis, which evaluated the impact of independent variables on the decision-making process regarding child vaccination.

Subjective barriers strongly drove the decision to refuse the vaccine in our analysis. The most prominent obstacle was the fear of adverse events. Respondents who cited safety concerns had 2.53 times higher odds of vaccine hesitation compared to women who reported no such barriers (OR=2.53; 95% CI 1.21–5.29; p=0.014). Missing a direct recommendation from a healthcare provider also proved critical, as it almost doubled the likelihood of refusal (OR=1.98; 95% CI 1.08–3.63; p=0.028).

We also noticed a marginal trend regarding educational background (OR=1.62; p=0.059). While this hints that a person’s academic level might shape their choice, it fell just short of the strict p <0.05 significance cutoff. Surprisingly, several variables we expected to be important failed to independently influence the decision in the multivariable model. Factors like baseline awareness of HPV (p=0.081), knowing about gender-neutral immunization (p=0.23), prior cervical screening (p=0.14), age group, and the respondent’s geographic cohort (Ukraine versus international) lacked statistical significance.

Ultimately, these results point to a necessary shift in how public health interventions are designed. Simply spreading general information about HPV or focusing on specific demographic groups appears insufficient. To actually improve vaccination uptake, strategies must directly dismantle safety myths and ensure that clinicians explicitly advise their patients to get vaccinated.

DISCUSSION

This study revealed a consistent paradox: Ukrainian women possess significantly higher HPV knowledge (88.7 vs 65.3%; p <0.001) and knowledge of gender-neutral vaccination (67.6 vs 48.6%; p=0.002), yet they report substantially more fear of side effects (39.2 vs 25.0%; p=0.03).

Our regression model points directly to fear as the heaviest drag on vaccination willingness (OR=2.53; 95% CI 1.21–5.29; p=0.014). We see this exact pattern frequently in the broader literature, where safety anxieties consistently emerge as the most pervasive global hurdle to immunization [15, 16].

This brings up an interesting contradiction in our data: if Ukrainian respondents are so well-informed, why do they display such intense anxiety? The roots of this problem likely run deep. Historical skepticism toward vaccines left over from the post-Soviet era certainly plays a part. Additionally, local public health messaging might be somewhat lopsided—pushing hard on the realities of cancer risk but failing to proactively calm fears about the vaccine’s safety profile. The fragility of the primary care network is another massive factor. Over a fifth (21.2%) of the women in Ukraine explicitly pointed to the lack of a doctor’s recommendation as their biggest roadblock, a stark contrast to the 8.3% seen in the international cohort (p=0.01). Clearly, having a physician personally endorse the shot can break through a patient’s hesitation [17, 23]. The WHO SAGE framework echoes this sentiment, positioning provider advice as a foundational pillar for vaccine acceptance [18].

When looking at the international participants, a completely different dynamic appeared. They knew less about HPV overall, yet they showed slightly more eagerness to vaccinate their children if the shots were free (81.9 vs Ukraine’s 75.8%; p=0.26). More strikingly, the frequency of reporting absolutely «no barriers» doubled in this group (36.1 compared to 17.7%; p <0.001). How does less knowledge translate to fewer hurdles? It seems that in certain environments, a baseline trust in the healthcare system or a general cultural acceptance of vaccines matters far more than knowing the specific clinical details of HPV. A. Krawczyk et al. drew a similar conclusion when they demonstrated how social norms and perceived risks heavily dictate patient intentions [20]. Another major difference was their media diet. Social platforms dominated as the primary source of medical information for the foreign respondents (26.4%, against just 10.9% in Ukraine; p=0.002). While this heavy reliance on digital media opens the door to dangerous misinformation, it simultaneously offers public health officials a direct channel for highly targeted interventions [8, 17].

We must also acknowledge the demographic skew here. Nearly 70% of the international cohort fell into the 18–25 age bracket (69.4%), a generational difference that almost certainly contributed to their overall lower perception of barriers.

However, even among young, educated women, only 48.6% knew that vaccination is recommended for boys — concerning given that peak infection occurs at age 15–19, and vaccination at age 9–14 produces a 2–3 times stronger immune response than in adults [13, 14]. The dramatic decline in protection against invasive cancer from 88% (when vaccinated at <17 years) to 53% (when vaccinated at >17 years) underscores the importance of preadolescent immunisation [13].

The HPV–breast cancer link, while not directly assessed in our questionnaire, provides a compelling rationale for expanding vaccination messaging. The meta-analysis by N.A. Salman et al. reported an odds ratio of 4.02 for high-risk HPV DNA in breast cancer tissue [5], and J.S. Lawson and W.K. Glenn proposed a causal mechanism involving lymphohematogenous spread [7]. N. Khodabandehlou et al. comprehensively reviewed the role of E6 / E7 oncoproteins in breast carcinogenesis [6]. This broader oncopreventive potential should be integrated into educational campaigns, particularly for women with a family history of breast cancer. The substantial mortality impact of achieving WHO elimination targets, as modelled by K. Canfell et al., further justifies aggressive vaccination policies [9].

Screening uptake was critically low in both groups (65.5 and 75.0% unscreened in 3 years), far below the WHO elimination target of 70% [11]. This deficit is particularly dangerous given that viral integration increases from 53.8% in CIN to 81.7% in invasive cancer [1]. In low- and middle-income countries, which account for 90% of global cervical cancer mortality, adolescent vaccination coverage remains as low as 3% [22], and a systematic review from Ethiopia confirmed that knowledge is the strongest predictor of acceptance [21].

The remarkably consistent finding that over 75% of women in both groups would vaccinate if free provides direct evidence that removing the financial barrier is a powerful policy lever. Priority immunisation of girls aged 9–14 can prevent 70% of HPV-associated neoplasias, making this the most pharmacoeconomically justified strategy [21, 22]. The 9-valent vaccine prevents 92% of HPV-associated cancers, and the presumptive approach changes the decision of 70% of initially hesitant parents [23].

Men are critical vectors: in 87% of couples, complete viral strain concordance drives persistent reinfections [19]. Gender-neutral vaccination can eliminate HPV-16 when 75% of adolescents of both sexes are covered, providing herd immunity [19]. Expanding the focus to include men is mutually beneficial, as preventing and treating HPV in males directly protects both sexes [19]. Another vulnerable group that warrants closer clinical surveillance includes solid organ transplant recipients. These patients face heightened susceptibility to the virus, yet the screening protocols applied to them still lack frustratingly uniformity [24].

Limitations. While our findings highlight stark differences in vaccine hesitation and awareness, we must interpret these results within the context of certain study constraints. A major consideration is the uneven distribution of our participants. The international group (n=72) was noticeably smaller than the Ukrainian one (n=293), potentially stripping the analysis of the statistical power needed to catch nuanced subgroup variations. Additionally, relying on digital outreach created an unavoidable selection bias. The individuals who ultimately completed the survey skewed younger, heavily urban, and highly educated. Because of this demographic tilt, it is difficult to confidently generalize our conclusions to rural residents or older generations who simply do not spend as much time online.

The makeup of the foreign cohort also complicates direct comparisons. This group was essentially a patchwork of respondents scattered across 12 different countries, with the bulk coming from Nigeria and Slovakia. Because of this geographic fragmentation, we can only treat these international results as an exploratory snapshot rather than a rigorous, country-by-country baseline. We also have to account for the flaws inherent in any survey design. When asking women about their Pap test history, there is always a lingering risk that social desirability or simple memory lapses altered the accuracy of their answers.

Moving forward, the scientific community needs longitudinal tracking. To truly grasp the evolving landscape of global HPV vaccine acceptance, future researchers will need to recruit massive, carefully stratified multinational cohorts and dig much deeper into granular socio-economic factors.

CONCLUSIONS

Ukrainian women have significantly higher HPV awareness (88.7 vs 65.3%) but also more fear of side effects (39.2 vs 25.0%). Fear is the strongest negative predictor of willingness (OR=2.53, p=0.014).

Screening uptake is critically low in both populations (65–75% unscreened in 3 years), far below WHO targets.

Willingness to vaccinate if free exceeds 75% in both groups, indicating that state-funded vaccination programs would likely achieve high coverage.

Social media as primary information source among international respondents (26.4 vs 10.9% in Ukraine) poses risks of misinformation.

Integrating information on the emerging HPV–breast cancer link into educational programs may further motivate vaccination.

Data availability statement: all data relevant to the study are included in the article.

Conflict of interest: the authors declare no conflict of interest.

Funding: this research received no specific grant from any funding agency.

Funding: this research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Use of artificial intelligence: in preparing this paper, the authors did not use any artificial intelligence tools to write the text, analyse data or create images. All stages of the research were carried out directly by the authors.

Competing interests: none declared.

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