Evaluation of the manuscript entitled “Policy Brief: An Evidence-Based Roadmap for the Equitable Elimination of HPV-Related Cancers by 2035” (ID: 173282). This policy brief synthesizes evidence to guide decision-makers in the fair elimination of HPV-related cancers.

The manuscript is well-written and addresses a topic of paramount importance in global public health. Below, I present my detailed evaluation according to the requested criteria, followed by specific recommendations to strengthen the work before its final indexing.

This policy brief is written and sound. The document synthesizes the most relevant evidence on HPV vaccination and screening and proposes a practical and equitable roadmap for the elimination of HPV-related cancers. The recommendations are aligned with WHO global strategies and the most recent scientific literature. I suggest minor modifications to strengthen its impact and applicability in resource-limited settings.

1. Conceptual Basis: Adequate

The conceptual framework is grounded in the WHO’s global strategy for the elimination of cervical cancer (90-70-90 targets). The authors correctly link oncogenic HPV infection as a necessary cause of cervical cancer and its relevance to other anogenital and oropharyngeal cancers.

2. Method: Adequate for the policy brief format.

As a policy brief, a detailed methodological description of systematic reviews is not expected. The authors cite the primary and secondary sources that support their claims, including meta-analyzes and clinical trials.

3. Alternative Solutions: Adequate, with opportunities for improvement. The recommendations are based on robust scientific evidence but could be strengthened with additional details on contextual implementation.

4. Conclusions: Adequate

The conclusions are derived from the evidence presented and are consistent with the document’s objectives.

5. Clarity and Organization: Adequate

The document is clear, concise, and well-structured, facilitating its reading by decision-makers.

Detailed Analysis and Recommendations for Improvement

1. Conceptual Basis (Adequate)

The authors correctly use the WHO framework for the elimination of cervical cancer, establishing the 90-70-90 targets as the guiding principle. The justification for addressing systemic inequities as the main barrier is well-founded.

Recommendation: Consider including an explicit reference to the definition of “elimination as a public health problem” (incidence <4 cases per 100,000 women-years) for greater conceptual precision.

2. Solution Alternatives (Adequate with Opportunities for Improvement)

a) Based on Scientific Results: Adequate

The authors appropriately cite:

- Meta-analysis by Drolet et al. (2019) on the population impact of vaccination

- KEN SHE trial on single-dose efficacy (correctly cited as Barnabas et al.)

- Meta-analysis by Arbyn et al. (2018) on the vaginal self-sampling methodology.

- Analysis by Stelzle et al. (2021) on risk in women with HIV

Suggestion for improvement:

The citation of the KEN SHE trial in the current manuscript (reference 4) appears as “Barnabas RV, Brown ER, Onono M, et al.: Single-dose HPV vaccination efficacy... study protocol...”. It would be preferable to cite the published results of the trial and not just the protocol. I suggest checking if there is a subsequent publication with definitive results and updating the reference.

b) Detailed description of the alternatives: Adequate, with room for improvement.

The authors present a three-year operational roadmap with specific actions for each year, which is a strength of the document. However, some areas could benefit from greater detail:

Single-dose vaccination: The single-dose schedule recommendation is appropriate and aligned with the 2022 WHO recommendations. It would be helpful to explicitly state that this recommendation applies to the general population, but that immunocompromised individuals (including women with HIV) require a two-dose schedule.

Vaccination in children: The childhood vaccination recommendation is correct and supported by growing evidence of individual and herd immunity benefits. However, the manuscript does not address specific implementation barriers for gender-neutral programs, such as incremental costs, cultural acceptability, and differentiated communication strategies. Including these considerations would strengthen the applicability of the recommendation.

Self-sampling screening: The evidence cited from Arbyn et al. is appropriate. It would be helpful to specify that the diagnostic accuracy applies specifically to PCR-based tests, not to all HPV tests.

Women with HIV: The claim of a “six times greater risk” is supported by Stelzle et al. It would be valuable to add that the WHO recommends starting screening in women with HIV at age 25 (not 30 as in the general population) and at more frequent intervals (every 3-5 years).

Community engagement strategies: The manuscript mentions “culturally sensitive community engagement strategies.” This could be enriched with concrete examples based on documented successful experiences, such as the use of Social and Behavior Change (SBC) in Nepal, which achieved 90% coverage through social listening, co-creation workshops, and the participation of community leaders.

c) Scientific sustainability of the alternatives: Adequate

The recommendations are supported by the best evidence, including mathematical models that show the impact on mortality and cost-effectiveness (Canfell et al., 2020; reference 12 in the manuscript). Including national investment and blended finance analyses is appropriate.

Suggestion: Consider citing cost-effectiveness studies in specific contexts, such as the analysis by Zou et al. (2020) in China, which shows the importance of vaccine price for economic return.

3. Strengths of the Manuscript

1. Focus on Equity: The emphasis on marginalized populations and women living with HIV is the document’s most valuable contribution.

2. Operational Roadmap: The three-year roadmap is practical and actionable for ministries of health. It would be worthwhile to break it down by strategies rather than by calendar time, as implementation will vary according to each country’s context, and actions can be started in parallel.

3. Monitoring Indicators: The inclusion of disaggregation by socioeconomic quintile, region, and HIV status is crucial for measuring equity.

4. Currency: The references are relevant and include recent literature.

4. Weaknesses and Areas for Improvement

Vaccination in Children: Lack of discussion on implementation barriers.

Include considerations on contextual cost-effectiveness, cultural acceptability, and communication strategies to overcome the perceived “feminization” of the vaccine.

Women with HIV: Generic recommendations without operational specificity. Specify age of initiation (25 years) and recommended intervals (every 3-5 years) according to WHO guidelines for WLHIV.

Emerging technologies: Limited mention of innovations.

Include reference to point-of-care tests and AI technologies such as Automated Visual Evaluation (AVE) that can facilitate implementation in resource-limited settings.

Community strategies: Generic description without concrete examples.

Incorporate documented experiences of community engagement, such as UNICEF’s SBC+ model in Nepal.

References: Protocol citation instead of results.

Verify and update the reference to the KEN SHE trial with published results.

Specific comments by section

Summary/Abstract: Excellent. Summarizes the problem, aim, and key recommendations.

Introduction

Appropriate and concise. Correctly establishes the context and justification.

Section 2.1 (Vaccination)

- The claim regarding single-dose efficacy (97.5% at 18 months) should cite the published results of the KEN SHE trial, not the protocol.

- I suggest adding: “Emerging evidence suggests that childhood vaccination not only contributes to herd immunity but also directly prevents oropharyngeal, anal, and penile cancers, the incidence of which is increasing.”

Section 2.3 (WLHIV and marginalized groups)

Strengthen with:

- “The WHO recommends that women with HIV screen at age 25, with 3-5 year intervals, given their elevated risk.”

- “Strategies such as integrating cervical cancer screening into chronic HIV care packages have proven effective in improving coverage in this population.”

Section 3.1 (Operational Roadmap)

Excellent structure. I suggest adding the following to Year 2: “Implement evidence-based community engagement strategies, such as the SBC+ (Social and Behavior Change) approach, which combines social listening, co-creation with communities, and participation of local leaders.”

Section 4 (Conclusions)

Appropriate and consistent with the findings.

References cited in this review

1. WHO. Global strategy to accelerate the elimination of cervical cancer as a public health problem. 2020.

2. Barnabas RV, et al. Single-dose HPV vaccination efficacy... Trials. 2021. (Ref 1)

3. Arbyn M, et al. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ. 2018. (Ref 2)

4. Stelzle D, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2021. (Ref 3)

5. Healthy Debate. HPV vaccination more than just women’s health issue. 2025.

6. SBIR.gov. Validation of a lab-free low-cost screening test... Automated Visual Evaluation. 2023.

7. Zou Z, et al. Domestic HPV vaccine price and economic returns... Lancet Glob Health. 2020. (Ref 4)

8. UNICEF Nepal. Listening, co-creating and connecting: SBC+ approaches for HPV vaccine. 2025.

9. PMC. Strategic approaches for global cervical cancer elimination. 2025. (Ref 5)

10. WHO Afro. Advancing the cervical cancer elimination agenda in the African region. 2024.

Does the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader?

Yes

Is the discussion on the implications clearly and accurately presented and does it cite the current literature?

Yes

Are the recommendations made clear, balanced, and justified on the basis of the presented arguments?

Partly

Reviewer Expertise:

Medical specialty in Clinical Infectious Diseases.Master's in Public HealthMaster's in EpidemiologyPhD in Epidemiology.Research area: Cervical Cancer and Human Papillomavirus Infection.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

This is an extremely well-written policy brief that succinctly summarizes all pertinent data and convincingly articulates the steps necessary for successful global implementation of HPV vaccination and cervical cancer screening to reduce cervical cancer morbidity and mortality. It is a quick read that is nevertheless comprehensive and lets the reader understand the stakes. I don't see any need for correction/revision.

Does the paper provide a comprehensive overview of the policy and the context of its implementation in a way which is accessible to a general reader?

Yes

Is the discussion on the implications clearly and accurately presented and does it cite the current literature?

Yes

Are the recommendations made clear, balanced, and justified on the basis of the presented arguments?

Yes

Reviewer Expertise:

cancer screening, shared decision making

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.