Gender-Neutral HPV Vaccination Could Prevent Thousands of RRP Cases, Study Finds

Original Study Published in PLOS ONE (October 14, 2025)
Study Authors: Hung-Hsueh Chou, Pen-Yuan Chu, Ying-Hui Wu, Casey Feng, Wei Wang, Isaya Sukarom, Andrew Pavelyev

For years, HPV vaccination programs around the world have primarily focused on protecting girls and young women from cervical cancer. These efforts have successfully reduced HPV-related disease in many countries. However, growing evidence suggests that vaccinating boys alongside girls may provide even greater public health benefits.

A recent study from Taiwan examined the potential impact of a gender-neutral HPV vaccination strategy, in which both boys and girls receive the 9-valent HPV (9vHPV) vaccine. Using a sophisticated disease transmission model that projected outcomes over 100 years, researchers found that vaccinating both sexes could substantially reduce HPV-related diseases, including recurrent respiratory papillomatosis (RRP).

For the RRP community, the findings are particularly noteworthy. The study projected that gender-neutral vaccination could prevent 3,880 cases of recurrent respiratory papillomatosis and reduce RRP-related deaths compared to a vaccination strategy focused solely on girls.

Study Abstract

Recurrent respiratory papillomatosis is a condition that occurs mainly in the pediatric population with a rate of 3.62 to 4.3 per 100,000 children. The most common clinical manifestation is dysphonia; however, the disease can progress to more severe forms, generating serious obstruction of the airway. A cross-sectional study was conducted in which patients diagnosed with laryngeal papillomatosis confirmed by histopathological analysis and polymerase chain reaction were included. The genotype of the virus and its viral load were determined through a search in the clinical records, and the clinical and genetic variables of each case were captured through a structured form. A total of 32 patients were enrolled, of which the prevalence of genotype 6 was found in 41% and the same prevalence in the case of genotype 11, with a percentage of coinfection with both subtypes of 18%. Genotype 11 was found to be associated with a greater number of resections (p = 0.004), a higher score on the Derkay scale (p = 0.02) and greater severity when presenting ≥ 4 surgeries per year and/or ≥ 10 total surgeries (p = 0.04). Human papillomavirus genotype 11 showed a greater association with the presentation of greater severity of recurrent respiratory papillomatosis in pediatric patients; therefore, this population is more susceptible to a poor outcome (which increases the demand for medical services), as well as impact on the quality of life of minors.

RRP Task Force Lay Summary

This modeling study simulates a dynamic transmission model over a 100-year period to compare vaccinating only girls versus both girls and boys with the 9-valent HPV vaccine in Taiwan. The methods involved calculating health impacts and costs based on realistic vaccination coverage rates and herd immunity. The findings indicate that including boys in the program, a gender-neutral vaccination approach, would provide significant additional protection. For males, this strategy is projected to prevent 3,880 cases of RRP, representing a nearly 16% reduction compared to the female-only strategy. It also predicted further decreases in cervical cancer and genital warts for females. Economically, the study found that a gender-neutral program would be highly cost-effective, saving over 1.5 billion New Taiwan Dollars in long-term disease management costs. The authors conclude that expanding vaccination to boys is a vital public health strategy that would substantially reduce the clinical and financial burden of HPV-related diseases across the entire Taiwanese population.

Why This Study Matters to the RRP Community

Much of the conversation around HPV vaccination focuses on preventing cervical cancer. While that benefit is critically important, HPV vaccination also has implications for several other diseases caused by HPV, including recurrent respiratory papillomatosis.

RRP is most commonly linked to HPV types 6 and 11, the same viral types responsible for most genital warts. Because the 9-valent HPV vaccine provides protection against these HPV strains, vaccination programs have the potential to reduce future cases of RRP at a population level.

This study provides one of the clearest demonstrations yet of how expanding vaccination to boys can further reduce the burden of HPV-related diseases beyond what is achieved through female-only vaccination programs.

A gender-neutral vaccination (GNV) strategy means offering HPV vaccination to both boys and girls before potential exposure to the virus.

Historically, many countries began with female-only vaccination (FOV) programs because of the strong link between HPV and cervical cancer. However, HPV also causes disease in males, including:

• Genital warts

• Head and neck cancers

• Penile cancer

• Anal cancer

• Recurrent respiratory papillomatosis

Vaccinating boys directly protects them from HPV-related diseases while also strengthening herd immunity throughout the population.

How the Researchers Conducted the Study

Rather than following real patients over many decades, researchers used a validated dynamic transmission model.

This type of model allows investigators to estimate:

• How HPV spreads through a population

• The impact of vaccination over time

• Future disease rates

• Healthcare costs

• Long-term public health outcomes

The model projected outcomes over a 100-year period and assumed:

• 85% vaccination coverage among girls

• 50% vaccination coverage among boys

• Lifelong vaccine protection

• Herd immunity effects

• Standard economic discounting methods

These assumptions allowed researchers to compare two scenarios:

Scenario 1

Female-only HPV vaccination

Scenario 2

Gender-neutral HPV vaccination

The differences between these two strategies revealed the additional benefits of vaccinating boys.

The RRP Findings Were Significant

For the RRP community, the most compelling finding was the projected reduction in recurrent respiratory papillomatosis cases.

Compared with female-only vaccination, the gender-neutral strategy was projected to prevent:

3,880 additional cases of recurrent respiratory papillomatosis

This represented:

A 15.8% reduction in RRP incidence among males

For a rare disease such as RRP, this level of reduction is substantial.

Every prevented case represents an individual who may avoid:

• Repeated surgeries

• Airway complications

• Voice difficulties

• Frequent medical appointments

• Long-term healthcare costs

Mortality Benefits Extended to RRP

The study also examined mortality associated with HPV-related diseases.

Researchers found that gender-neutral vaccination produced:

• A 14.1% reduction in male RRP-related deaths

• A 10.7% reduction in female RRP-related deaths

While RRP is often described as a benign disease, severe complications can occur. Reducing both disease incidence and mortality highlights the broad public health value of HPV prevention efforts.

Benefits Extended Far Beyond RRP

The impact of gender-neutral vaccination was not limited to recurrent respiratory papillomatosis.

The model projected substantial reductions in several HPV-related diseases.

Among Women

Compared to female-only vaccination, the gender-neutral strategy prevented:

• 572 additional cervical cancer cases

• 6,463 additional cases of cervical intraepithelial neoplasia (CIN)

• 57,691 additional cases of genital warts

• 229 additional cervical cancer deaths

Among Men

Researchers projected prevention of:

• 26 penile cancer cases

• 179,207 genital wart cases

• 4,955 head and neck cancer cases

• 3,880 RRP cases

These findings reinforce the reality that HPV is not solely a women's health issue. The virus affects people of all sexes, and prevention strategies can benefit entire populations.

The Economic Case Was Strong

Healthcare policymakers often ask whether vaccination programs are worth the investment.

This study suggests the answer is yes.

Researchers estimated that gender-neutral vaccination would save:

NTD 1.57 billion in disease management costs

over the modeled period.

Importantly, nearly half of those cost savings were attributable to diseases caused by HPV types 6 and 11, the same strains most commonly associated with RRP.

The analysis found that the strategy remained cost-effective even when researchers varied assumptions about:

• Vaccine pricing

• Vaccination rates

• Treatment costs

• Duration of protection

This consistency strengthens confidence in the study's conclusions.

Why Herd Immunity Matters

One reason gender-neutral vaccination performed so well in the model is the effect of herd immunity.

When more individuals are protected against HPV:

• Viral transmission decreases

• Fewer infections occur

• Population-level disease rates decline

Vaccinating boys not only protects boys themselves but also contributes to reducing HPV circulation throughout the broader community.

This creates additional indirect protection for individuals who remain unvaccinated or who have not developed full immunity.

Implications for Global HPV Vaccination Programs

Although this study focused on Taiwan, its findings contribute to a growing body of international evidence supporting gender-neutral HPV vaccination.

The authors note that similar results have been reported in countries including:

• Spain

• Italy

• Hong Kong

Across these settings, researchers consistently found that including boys in HPV vaccination programs produces additional reductions in HPV-related disease and remains economically justified.

For countries currently considering expansion of HPV vaccination programs, these data provide valuable evidence that benefits extend far beyond cervical cancer prevention alone.

Important Limitations

Like all modeling studies, this research has limitations.

The model:

• Did not include every possible health benefit of vaccination

• Did not evaluate catch-up vaccination programs

• Did not account for all indirect economic costs

• Relied on assumptions about vaccine uptake and long-term protection

Because the study projects future outcomes rather than observing actual patients over 100 years, the results should be viewed as estimates rather than guarantees.

However, the model was based on established epidemiological methods and produced findings consistent with other international studies.

What This Means for Patients and Families

For individuals affected by recurrent respiratory papillomatosis, this study reinforces an important message: HPV vaccination has the potential to reduce future cases of RRP on a population level.

While vaccination is primarily a preventive tool and not a treatment for established disease, widespread vaccination may help decrease the number of children and adults who develop RRP in the future.

The findings also highlight the importance of considering HPV prevention as a public health strategy that benefits everyone, not just one segment of the population.

Key Takeaways

• Researchers compared female-only HPV vaccination with gender-neutral vaccination in Taiwan.

• The study projected outcomes over a 100-year period using a validated transmission model.

• Gender-neutral vaccination was projected to prevent 3,880 cases of recurrent respiratory papillomatosis.

• Male RRP incidence decreased by approximately 15.8% compared with female-only vaccination.

• RRP-related deaths were also reduced under the gender-neutral strategy.

• Significant reductions were projected for genital warts, cervical cancer, penile cancer, and head and neck cancer.

• The strategy saved more than NTD 1.5 billion in disease management costs.

• Researchers concluded that vaccinating both boys and girls would provide meaningful public health and economic benefits.

Frequently Asked Questions

What is gender-neutral HPV vaccination?

Gender-neutral vaccination refers to HPV vaccination programs that include both boys and girls rather than focusing exclusively on girls.

How is HPV connected to recurrent respiratory papillomatosis?

Most RRP cases are caused by HPV types 6 and 11. Preventing infection with these HPV types may help reduce future RRP cases.

Did this study examine actual patients?

No. This was a modeling study that used a validated disease transmission model to project outcomes over a 100-year period.

How many RRP cases could be prevented?

The researchers projected that gender-neutral vaccination could prevent 3,880 cases of recurrent respiratory papillomatosis compared with a female-only vaccination strategy.

Was gender-neutral vaccination cost-effective?

Yes. The study concluded that vaccinating both boys and girls with the 9-valent HPV vaccine would be cost-effective in Taiwan and would generate substantial long-term healthcare savings.