Human papillomavirus (HPV) is the most prevalent non-HIV sexually transmitted infection (STI) globally, and most sexually active individuals will acquire HPV during their lifetime [1-3]. Among women, persistent infection with high-risk oncogenic HPV types is a necessary cause of cervical cancer. It contributes to a broader spectrum of anogenital and oropharyngeal cancers, creating a substantial preventable burden across the life course [3-5]. HPV vaccination offers a critical opportunity for primary prevention of an STI-related cancer, with high efficacy against vaccine-type infection and intraepithelial neoplasia when administered before exposure [5-7]. Among young adult women beyond routine childhood immunization schedules, HPV vaccination is often positioned as a preference-sensitive decision requiring individualized counseling, yet vaccine coverage remains insufficient in many settings [8,9].

Incomplete vaccine uptake reflects both individual-level barriers (knowledge, attitudes, and motivation) and structural barriers (access, cost, and provider recommendation). While system-level changes are essential, individual-level educational interventions remain necessary to address modifiable cognitive and motivational barriers, particularly in contexts where structural access exists but is underused [9,10]. Individual barriers include limited awareness and misinformation, perceived stigma associated with STI prevention, low confidence in vaccine safety, concerns about fertility and long-term harms, and the “intention-behavior gap,” the well-documented phenomenon in which individuals express willingness yet do not translate intention into action [11-13]. These factors are particularly relevant for women’s health in culturally conservative contexts where sexual health discussions carry social stigma.

In Saudi Arabia, cervical cancer incidence is comparatively low but nonnegligible: the Information Centre on HPV and Cancer (ICO)/International Agency for Research on Cancer (IARC) country fact sheet [14] estimates approximately 358 new cases and approximately 179 deaths annually, with an age-standardized incidence rate (ASR) of approximately 2.8 per 100,000 women and ranking eighth among cancers in women overall and in those aged 15 to 44 years. Recent registry-based analyses also show regional variation, with Makkah consistently reporting the highest rates, followed by Riyadh and the Eastern Region, and a favorable shift toward earlier stage at diagnosis between 2005 and 2019 (increase in localized-stage diagnoses; decline in unknown stage), underscoring geographic and stage heterogeneity relevant to prevention strategies [15,16]. The Saudi Cancer Registry (under the National Cancer Center, Saudi Health Council) continues to publish periodic incidence reports and program updates, improving data quality for planning and evaluation [17].

Regarding vaccine policy and access, the Saudi Ministry of Health (MOH) health-education pages recommend HPV vaccination for adolescents (girls and boys) at ages 11 to 12 years (can start at age 9 years) and catch-up through age 26 years, aligning with international guidance; adults aged 27 to 45 years may benefit on a case-by-case basis. Since 2022, public communications from MOH and independent evaluations have described school-based campaigns introducing HPV vaccination for early adolescents, with media notices highlighting the importance of early vaccination and a multicohort school-based rollout reported in 2022 (with subsequent years’ activity). Importantly, official, centralized MOH fee schedules for HPV vaccine are not published; doses delivered within school-based/public programs are provided at no charge to families, whereas private-sector prices are not standardized or publicly listed by MOH/Saudi Food and Drug Authority (SFDA) [18].

Contemporary studies in Saudi Arabia consistently demonstrate low HPV vaccine uptake despite rising awareness. For example, a 2023-2024 national survey found that although 60.85% of Saudi women had heard of HPV, only 8.25% had received the vaccine, and more than 70% expressed willingness, highlighting a clear intention-behavior gap [19]. Similarly, recent cross-sectional research shows that Saudi women continue to report fear of side effects, doubts about vaccine effectiveness, and low positive perceptions, indicating persistent informational and motivational barriers to HPV prevention efforts [20]. Among younger populations, such as nursing and medical students, studies report poor HPV knowledge, limited understanding of screening, and low vaccination rates, with over 70% unvaccinated, despite relatively high awareness [21,22].

Although overall awareness has significantly increased following Saudi MoH campaigns, HPV-related behaviors remain suboptimal. A national comparison from 2022 to 2024 documented a rise in HPV awareness from 38.8% to 71.1%, yet cervical cancer screening uptake remained low, with only 25.8% of women reporting ever having a Pap smear [23]. Cultural and social dynamics further shape preventive behaviors: barriers such as perceived lack of necessity, abstinence-based reasoning, safety concerns, and misconceptions about who the vaccine is “appropriate” for continue to impede uptake [24]. In family-centered decision contexts, parental acceptance of HPV vaccination is strongly influenced by education level, health care worker status, and especially receiving a recommendation from the MoH or clinicians, demonstrating how social and institutional cues shape women’s access to preventive care [24-26].

Shared decision-making (SDM) principles may require adaptation in this context, as women’s health care decisions often involve family consultation and are influenced by clinician paternalism [27-29]. Educational interventions can support SDM by strengthening women’s knowledge and confidence to engage in vaccine discussions, ask questions, and express preferences to clinicians [30,31]. Therefore, this study aims to improve determinants of informed vaccination decisions, a foundational step toward SDM-compatible counseling.

Educational interventions have repeatedly demonstrated effectiveness in improving HPV-related knowledge, attitudes, and vaccine acceptance [11,32]. However, many interventions lack cultural tailoring and do not address context-specific concerns such as fertility misconceptions, stigma, and family influence, and they often fail to incorporate behavioral theory to explain how information converts to lasting motivation and action [11,33,34]. Ensuring equitable reach requires evaluating whether interventions maintain effectiveness across differing levels of health literacy, as literacy-related disparities substantially affect the ability to process health information and may reduce the intervention’s public health impact [35-37].

The information-motivation-behavioral skills (IMB) model proposes that behavior change is driven by accurate, actionable information, motivation (personal and social), and the behavioral skills needed to execute decisions, an especially relevant structure for vaccine uptake behaviors that require navigating appointments, consent, and follow-through [38,39]. IMB-based educational interventions have improved HPV vaccination-related outcomes in other contexts, including web-based education among female college students [40]. Yet, within Saudi Arabia and the broader Middle Eastern region, many studies remain cross-sectional, focus on university settings, or assess knowledge and hesitancy without testing scalable, culturally adapted, primary care–compatible intervention models [20,41]. Additionally, registry and international sources emphasize that although overall cervical cancer incidence is low, regional disparities and ongoing cases justify prevention efforts, particularly in high-population regions such as Makkah and Riyadh.

This study addresses these gaps directly by evaluating a culturally tailored educational intervention to improve HPV vaccination decision-making among women in Northern Saudi Arabia. This study makes 3 distinct contributions. First, it addresses HPV vaccination as both an informational challenge and an SDM implementation challenge, where women’s concerns, stigma, and family/social context must be addressed to support informed and values-concordant decisions [27,29,30]. Second, it applies a behavioral theory lens (IMB) to structure how education targets the specific mechanisms most plausibly linked to vaccine initiation behaviors [38,39]. Third, it focuses on a Saudi setting where published evidence indicates persistent gaps in knowledge and uptake and where culturally tailored prevention strategies are needed to reduce HPV-related disease burden among women [4,19,20]; contemporaneous national and international data further justify the focus, citing current case counts, regional variation, and active public health efforts.

Research question 1 assesses whether a culturally tailored, IMB-based educational intervention improves HPV-related knowledge, health awareness, attitudes, and vaccination intentions among women in Northern Saudi Arabia compared to standard care. Research question 2 assesses whether intervention effects are sustained at 3-month follow-up. Research question 3 assesses whether intervention effects vary by age, education level, health literacy, or prior vaccination experience.

Hypothesis 1 states that intervention participants will demonstrate significantly greater improvements in all 4 outcome domains compared to controls at post-intervention and 3-month follow-up. Hypothesis 2 states that effects will be sustained (no significant decay) between postintervention and 3-month assessments. Hypothesis 3 states that intervention effects will not significantly differ across demographic subgroups (consistent effectiveness).

A quasi-experimental design (pretest-posttest with a control group), with a pragmatic, nonrandomized allocation approach, was used due to operational constraints within the primary health care (PHC) system that precluded individual-level randomization, combined with concerns about contamination between intervention and control participants within the same clinic sessions. Outcomes were assessed at 3 time points: baseline (T1), approximately 1 week after the intervention session (T2), and 3 months after baseline (T3). The study is reported in accordance with the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) statement for nonrandomized evaluations of behavioral and public health interventions; a completed TREND checklist is provided in Multimedia Appendix 1. Causal language is used cautiously given the nonrandomized design, and effect estimates are interpreted as associations consistent with an intervention effect.

Sample size was estimated using G*Power 3.1 for repeated-measures ANOVA with within-between interaction. The primary test was the F test of the group × time interaction in a 2 (group) × 3 (time) mixed design, for which the test statistic follows a noncentral F distribution with numerator df = (2 − 1)(3 − 1) = 2 and denominator df = 2(N − 2), with sphericity assumed (ε=1). Assuming a moderate effect size (F=0.25, equivalent to Cohen d≈0.50), an α of .05, power of 0.80, a total of 3 measurement time points, and a within-subject correlation of 0.5, the sample size required was 82 participants per group. Anticipating 20% attrition, we targeted 103 per group (n=206). Actual enrollment (n=389) substantially exceeded this target, providing adequate power for primary analyses.

Although the achieved sample provides sufficient power for main effects, the exploratory subgroup analyses (Statistical Analysis section) were not formally powered and should be interpreted as hypothesis-generating: interaction tests require approximately 4 times the sample size of main-effect tests, and with 190 participants per group, statistical power for detecting subgroup interactions was estimated at 40% to 50%.

At baseline (T1), participants provided written informed consent and completed the Arabic questionnaire in a private PHC room (approximately 20 to 25 minutes). Trained female research assistants were available to clarify procedural questions without guiding responses.

At T2, a mean of 6.8 (SD 1.2) days after the intervention session (approximately 1 week after baseline), both groups completed the same questionnaire using identical paper-based, in-person administration procedures.

At T3, approximately 3 months postbaseline (mean 91.4, SD 8.6 days), follow-up data were collected via standardized telephone interviews conducted by trained female staff. T3 telephone interviewers were partially blinded: they did not know participant group allocation at the time of the call but could potentially infer group status if participants spontaneously mentioned attending an education session. To minimize detection bias, interviewers used scripted questions, avoided unstructured conversation, and were trained to redirect discussion to assessment items if participants volunteered unsolicited information about study participation.

To assess potential mode effects (in-person paper vs telephone), we conducted sensitivity analyses comparing T2 (paper) vs T3 (telephone) response patterns within the control group, which received no intervention between these time points. No significant differences were observed (all P>.15), suggesting minimal mode-related bias (Multimedia Appendix 5).

All statistical analyses were performed using R software (version 4.3.1; R Core Team), following a prespecified analysis plan.

Ethical approval for this study was granted by the Local Committee of Bioethics at Northern Border University (HAP-09-A-043; decision number 90/25/H). All participants were informed about the study objectives and procedures, and written informed consent was obtained before participation. The research team adhered strictly to all bioethics guidelines stipulated by the committee throughout the study.

Consent procedures emphasized voluntariness, confidentiality, the right to withdraw, and the possibility of discomfort when discussing sensitive topics. Consent forms were written in Arabic at approximately a sixth-grade reading level (assessed using the Arabic SMOG formula) and reviewed orally by female staff to ensure comprehension.

Confidentiality was maintained using unique IDs, separate secure storage of identifiers and data, encrypted password-protected databases, and staff confidentiality training. Data will be retained for 5 years and then securely destroyed by institutional policy.

Risk mitigation strategies included female-only delivery teams, private spaces, flexible scheduling, permission to skip any question, and cancer-prevention framing to minimize stigma. Adverse events were monitored through participant self-report at each assessment and facilitator incident reports. No adverse events were reported. Control participants were offered delayed access to the intervention after completion of the 3-month follow-up (148/190, 78% accepted).

This nonrandomized interventional study was not registered in a public trials registry because trial registration is not a requirement for quasi-experimental evaluations under applicable journal policy; the analysis plan was prespecified in writing before data analysis. Study methods and procedures were reviewed and approved by the institutional bioethics committee; no protocol amendments were made after data collection began.

A total of 512 women were assessed for eligibility between December 2025 and May 2026 in the 4 participating PHCs. Of these, 123 (24%) were excluded: 69 did not meet inclusion criteria (18 were currently pregnant, 28 were health care professionals or trainees with specialized knowledge, 4 had cognitive impairment limiting informed consent, and 19 had previously completed the full HPV vaccination series), 32 declined to participate, and 22 were excluded for other reasons (eg, planned relocation or inability to attend scheduled sessions). The remaining 389 women (76% of those screened) were enrolled and allocated to the educational intervention group (n=194) or the control group (n=195; Figure 1). All 380 participants included in the analytic sample completed the 3-month follow-up; the final follow-up assessment was completed on May 30, 2026.

In the intervention group, 99% (192/194) of enrolled participants received the educational intervention; 2 participants withdrew before the intervention session because of scheduling conflicts. In the control group, 97.9% (191/195) of enrolled participants completed the baseline assessment and remained in the study; 4 participants withdrew before follow-up assessments could begin (2 because of relocation and 2 because they could not be reached). During follow-up, an additional 2 participants from the intervention group and 1 from the control group were lost to follow-up (lost contact or declined further assessment). Consequently, 190 participants per group (380/389, 97.7%) completed all 3 assessments and constituted the analytic sample (Figure 1). Baseline characteristics did not differ significantly between completers and those lost to follow-up (all P>.40), suggesting minimal attrition bias.

Baseline demographic, socioeconomic, and health-related characteristics were well-balanced between the study arms (Table 1). The mean age of participants was approximately 28.6 (SD 6.9) years, with the majority holding a university degree (n/N, 65%). Approximately 43% (n/N) of participants were married. Importantly, potential confounders such as health literacy, previous vaccination experience, and family history of cervical cancer showed no statistically significant differences between groups (all P>.05). Standardized differences for all covariates were less than 0.10, indicating minimal observed baseline imbalance despite nonrandom allocation and supporting comparability of groups for adjusted analyses.

Baseline outcome scores were also well-balanced: mean knowledge scores were 2.97 (intervention) vs 2.94 (control), health awareness 3.05 vs 2.93, attitude 2.92 vs 2.91, and vaccination intentions 3.99 vs 3.98 (all P>.40, standardized differences <.10). This balance across both baseline characteristics and outcome measures strengthens causal inference despite the nonrandomized design.

Linear mixed-effects models were fitted for all primary outcomes to address potential baseline imbalance and confounding (Table 2). Three nested models were compared: model 0 (unadjusted), model 1 (adjusted for age, education, and marital status), and model 2, the primary model (additionally adjusted for health literacy, previous vaccination experience, and family history of cervical cancer).

The intervention effect (time × group interaction) was statistically significant across all adjusted models and across all 4 outcomes at T2 and T3. Adjustment for covariates produced minimal attenuation of effect estimates (β coefficients changed by <0.03 across models), indicating strong baseline balance and little measured confounding. Model R² values ranged from 0.12 to 0.28, with the fully adjusted models providing the best fit (Multimedia Appendix 6). Model diagnostics confirmed the adequacy of the linear mixed models: residual plots showed no systematic patterns; Q-Q plots indicated approximately normal residuals; and all VIFs were <2.5.

Because the intervention was delivered in groups (10-15 participants) across multiple sessions (n=40), clinics (n=4), and facilitators (n=8), clustering of responses could have occurred. To address this concern (raised in BZ Major Comment 2), sensitivity models were refitted with random intercepts for clinic and intervention sessions, and with cluster-robust (sandwich) standard errors applied to the primary complete-case models. ICCs were modest at clinic and session levels (range 0.01-0.05). The cluster-adjusted models produced slightly larger point estimates and slightly wider confidence intervals than the primary models (maximum difference in β of ±0.04 for any outcome or time point), and all previously significant effects remained significant (P<.01). These analyses indicate that clustering does not materially alter inference for the primary outcomes.

To quantify the specific magnitude of the intervention effect, within-group change scores were calculated and compared directly between groups. Table 3 presents immediate postintervention changes (T2 – T1) as well as sustained changes at 3-month follow-up (T3 – T1).

At the immediate postintervention assessment, the intervention group achieved significantly greater gains than controls for health awareness (P=.05; d=0.21) and vaccination intentions (P=.001; d=0.34). Knowledge and attitudes showed positive trends that did not reach statistical significance at this early time point. However, by the 3-month follow-up, all 4 outcomes demonstrated significant between-group differences in change scores, with effect sizes ranging from d=0.45 (knowledge) to d=0.82 (intentions) using the change score pooled SD. The progressive strengthening of effects from postintervention to follow-up suggests sustained engagement with intervention content and potential social diffusion or reinforcement of learning over time.

Exploratory subgroup analyses were conducted to determine whether intervention effects varied by key demographic characteristics. We assessed interactions between the intervention and 4 prespecified moderators: age (18-26 years vs 27-45 years), education level (university vs below university level), health literacy (inadequate/marginal vs adequate using validated cutoffs), and previous vaccination experience (any vs none). Moderator effects were evaluated using 3-way interaction terms (time × group × moderator) in the mixed-effects models. Because time (2 levels), group (2 levels), and each moderator (2 levels) were binary, each interaction term has 1 numerator degree of freedom; denominator degrees of freedom were estimated using the Satterthwaite approximation. Using a Bonferroni-corrected significance level of α=.0125 per outcome domain (to account for testing 4 moderators separately), no significant 3-way interactions (time × group × moderator) were detected for any outcome.

For vaccination intentions (the outcome with strongest main effects), the interaction tests were: age (F_1,424.31=1.23; P=.28), education (F_1,421.05=0.87; P=.42), health literacy (F_1,418.52=1.41; P=.23), and prior vaccination experience (F_1,425.14=0.65; P=.52). Similar nonsignificant patterns were observed for other outcomes (Multimedia Appendix 6 provides complete stratified results and interaction statistics).

Point estimates suggested numerically larger gains for younger women (age 18-26 years: mean 3-month change +1.10, 95% CI 0.89-1.31 vs age 27-45 years: mean 3-month change +0.98, 95% CI 0.72-1.24), university-educated participants (+1.15, 95% CI 0.96-1.34 vs below university level: +0.92, 95% CI 0.65-1.19), and those with adequate health literacy (+1.18, 95% CI 0.99-1.37 vs inadequate/marginal: +0.89, 95% CI 0.64-1.14), but these differences were not statistically significant after multiplicity correction. The study was not formally powered for interaction tests (estimated power approximately 40%-50%); therefore, the absence of significant interactions should not be interpreted as evidence of equal effect magnitudes across subgroups, and these analyses are best treated as hypothesis-generating.

The control group also showed small increases across outcomes, particularly for vaccination intentions (from 3.98 at T1 to 4.15 at T3). Possible explanations discussed transparently include secular trends from concurrent national HPV awareness campaigns in Saudi Arabia, repeated measurement effects (familiarity with questionnaire items), and nonspecific attention during routine clinic visits within the time period. Although these changes were small and did not reach statistical significance in isolation, the primary inference is based on adjusted between-group comparisons that account for any incremental control arm change.

Comprehensive sensitivity analyses confirmed the robustness of primary findings across alternative analytic approaches (see Multimedia Appendix 4 for complete results). Intention-to-treat analysis using LOCF for the 9 participants lost to follow-up yielded effect estimates within 0.02 to 0.04 points of primary complete-case results, with all previously significant effects remaining significant (all P<.01).

Per-protocol analysis restricted to participants with 80% or greater session attendance (n=352; 92.7% of analytical sample) showed slightly stronger intervention effects, with β coefficients 5% to 8% larger than primary models (eg, vaccination intentions at 3 months: β=0.93, 95% CI 0.66-1.20 vs primary β=0.86). This dose-response pattern is consistent with greater engagement producing larger effects.

Multiple imputation with 50 datasets using MICE produced point estimates within 0.01 to 0.03 points of complete-case analysis, with nearly identical CIs and P values. Alternative covariance structures (unstructured and first-order autoregressive) yielded substantively identical conclusions (maximum difference in β=0.02; all previously significant effects remained P<.001).

Assessment of potential mode effects (in-person paper administration vs telephone) revealed no systematic bias. Within the control group (which received no intervention between T2 and T3), responses at T2 (paper) and T3 (telephone) showed no significant differences across all 4 outcomes (all P>.15; mean absolute difference <.08 points; Multimedia Appendix 5). This provides reassurance that the T3 telephone data collection mode did not introduce measurement artifacts. The consistency of findings across these diverse sensitivity analyses reinforces the internal validity and robustness of the trial results.

This study demonstrates that a culturally tailored, IMB-based educational intervention significantly improved HPV-related knowledge, health awareness, attitudes, and vaccination intentions among women aged 18 to 45 years attending PHC centers in Northern Saudi Arabia. At 3-month follow-up, intervention participants showed medium-to-large effect-size improvements across all outcomes compared with controls, with effects sustained from the immediate postintervention assessments. These findings contribute to the limited evidence base on culturally tailored HPV education interventions in Middle Eastern contexts and provide the first controlled evaluation of an IMB-based approach delivered in Saudi primary care settings, but because allocation was nonrandom and based on clinic session timing, the present results estimate intervention association rather than a strict causal effect.

The intervention yielded a substantial rise in vaccination intention, from 3.99 at baseline to 5.04 at the 3-month follow-up, representing a 15% absolute increase on a 7-point scale and constituting the largest observed effect, a pattern consistent with prior educational interventions. Similar gains have been documented among pregnant women in Saudi Arabia, where structured educational sessions produced twofold to threefold increases in HPV-related awareness [48]. Comparable outcomes were also observed among Tunisian female students, who demonstrated significant knowledge improvement following brief video-based instruction, with mean scores rising from 4.23 preintervention to 6.16 postintervention, and vaccination acceptance reaching 68.4% [49]. These findings together suggest that theory-driven educational strategies addressing cultural concerns can produce reliably positive effects across Middle East and North Africa populations.

Our observed knowledge gains, rising from 2.97 at baseline to 3.74 at follow-up, mirror results from Chinese college populations who participated in web-based IMB model interventions, where significant increases in HPV knowledge and motivational determinants were consistently reported [40,50,51]. However, a key contrast emerges despite marked improvements in knowledge and intention: Chinese studies reported very limited translation into actual vaccine uptake, a gap attributed to systemic barriers such as high vaccine cost and restricted insurance coverage [52]. This intention-behavior discrepancy highlights that, although educational interventions can effectively enhance cognitive and motivational precursors to vaccination, their population-level impact ultimately depends on structural factors, including affordability, vaccine access, and provider recommendation practices.

Not all educational interventions achieve sustained behavioral impact. Systematic reviews of HPV vaccine education indicate that knowledge gains do not invariably translate into vaccination intentions or uptake, particularly when interventions fail to address context-specific motivational barriers such as perceived stigma, safety concerns, or family opposition [11]. Moreover, intention effects observed at short-term follow-up (1-3 months) often decay by 6 to 12 months absent booster sessions or reminder systems [13]. Our 3-month results should therefore be interpreted as promising but preliminary, requiring longer-term follow-up with objective vaccination outcomes to confirm durability and behavioral translation.

The intervention’s effectiveness supports IMB model predictions that targeting all 3 constructs, information, motivation, and behavioral skills, produces more robust effects than information-only approaches [38]. The information component addressed widespread misconceptions (HPV/HIV confusion, infertility concerns, and Halal permissibility) and provided evidence-based content on vaccine safety and efficacy, yielding significant knowledge gains. The motivational component emphasized cancer prevention framing rather than STI prevention to reduce stigma, addressed personal susceptibility and severity perceptions, and normalized vaccination within cultural contexts, resulting in improved health awareness and attitudes. The behavioral skills component strengthened self-efficacy, communication competencies for discussing vaccination with providers and family members, and problem-solving for navigating appointment systems, contributing to the substantial intentions effect.

Notably, the progressive increase in intentions from postintervention (4.65) to 3-month follow-up (5.04), rather than decay, suggests that behavior change processes may require extended periods for consolidation as individuals integrate new information, negotiate social contexts, and build decision-making confidence. This temporal pattern aligns with IMB-based intervention studies reporting that behavioral skills acquisition requires longer maturation periods than informational or motivational gains [40].

The moderate-to-large effect sizes observed in this study compare favorably with meta-analytic estimates for health education interventions and exceed typical effects for single-session interventions [33]. Several design features likely contributed to effectiveness: (1) cultural adaptation through systematic formative research addressing local barriers (STI stigma, fertility concerns, and family decision-making dynamics), (2) theoretical grounding ensuring comprehensive coverage of behavioral determinants, (3) female-only facilitation enhancing comfort with sensitive topics, (4) interactive group format promoting social normative influences, and (5) high implementation fidelity (93%) maintaining intervention integrity.

This study has several methodological strengths. First, the intervention was grounded in behavioral theory (IMB model) and developed through systematic cultural adaptation involving formative research with target populations and stakeholders, enhancing both internal validity and local relevance. Second, the study achieved excellent retention (97.7%) across 3 time points, allowing assessment of both immediate and sustained effects. Third, despite nonrandomized allocation, baseline balance across measured covariates (standardized differences <.10) and comprehensive covariate adjustment strengthen confidence in effect estimates. Fourth, high implementation fidelity (93% adherence; substantial interrater reliability κ=0.78) and standardized delivery protocols support replicability. Fifth, the primary care setting and focus on adult women, an underserved population in HPV vaccination research, enhance ecological validity and policy relevance. Finally, comprehensive sensitivity analyses (intention-to-treat, per-protocol, multiple imputation, and alternative covariance structures) confirmed robustness of findings across analytic approaches.

Several limitations qualify the interpretation and generalizability of findings.

Future research should address the following priorities.

This study provides evidence that a culturally adapted, IMB-based educational intervention delivered in Saudi primary care settings significantly improves HPV-related knowledge, health awareness, attitudes, and vaccination intentions among women aged 18 to 45 years, with medium-to-large effect sizes sustained at 3-month follow-up. Effects were consistent across age, education, and health literacy subgroups, suggesting broad applicability. These findings demonstrate that educational interventions targeting cognitive and motivational barriers are feasible, acceptable, and effective in conservative Middle Eastern contexts where HPV vaccination faces cultural sensitivities.

Nevertheless, these results suggest that educational interventions represent a necessary, though insufficient, component of comprehensive HPV prevention strategies. HPV-related cancers are preventable, yet barriers persist at individual, interpersonal, health care system, and policy levels. Closing the gap between vaccine availability and uptake requires multilevel interventions that simultaneously address knowledge, motivation, structural barriers, and cultural realities. This study represents an important step toward evidence-based, culturally grounded HPV prevention programs that can contribute to cervical cancer reduction and women’s health equity in Saudi Arabia and throughout the Middle Eastern region.