Twenty years ago, a major milestone in cancer prevention was reached when the US. The FDA approved the first human papillomavirus (HPV) vaccine. Introduced in 2006, the quadrivalent vaccine protected against HPV types 16 and 18, which are responsible for most HPV-related cancers, as well as HPV types 6 and 11, which cause genital warts but have low oncogenic potential.

Approval was followed in Italy in 2007 and was subsequently extended to many countries worldwide.

Over the past two decades, HPV vaccination has evolved substantially with newer vaccine formulations and updated schedules. However, despite clear evidence of effectiveness and safety, vaccination coverage remains below target levels in many countries. Persistent disparities in access, awareness, and uptake continue to limit the full public health impact of vaccination, according to Karen Canfell, PhD, from the Cancer Elimination Collaboration, Sydney School of Public Health, University of Sydney, Sydney, Australia, who discussed the issue in a commentary published in Nature Medicine.

HPV and Cervical Cancer

Canfell focused on the role of vaccination in preventing cervical cancer. She noted that in cancer prevention, the strength and impact of the causal relationship between HPV and cervical cancer are matched only by those between tobacco use and lung cancer and other cancers.

The link between HPV infection and cervical cancer is well established. More than 200 HPV types have been identified, but only one subset is oncogenic and increases cancer risk. HPV types 16 and 18, which are included in all currently available vaccines, account for most cervical cancer cases. Cervical cancer is a significant public health concern in Italy.

The global burden of cervical cancer is substantial. According to GLOBOCAN estimates, more than 662,000 cases and nearly 349,000 deaths were reported worldwide in 2022, with the greatest impact seen in low- and lower-middle-income countries. The consequences often extend beyond the health sector, becoming a broader social challenge. Each year, more than 200,000 children lose their mothers to cervical cancer, with serious consequences for their survival and education because the disease often affects women during their most productive years.

Canfell described the elimination of cervical cancer as a scientifically grounded and achievable goal, arguing that it extends beyond public health challenges to become a matter of human rights.

World Health Organization (WHO) Strategy

The WHO adopted its global strategy for cervical cancer elimination in 2020.

The initiative is unprecedented in its ambition to eliminate cancer through vaccination, screening, and treatment.

Elimination is defined as reducing cervical cancer incidence to fewer than four cases per 100,000 women annually.

To remain on track toward this goal, WHO established the 90-70-90 targets:

• 90% of girls fully vaccinated against HPV by age 15.
• 70% of women screened with a high-performance test, such as an HPV DNA test, by ages 35 and 45
• 90% of women with precancerous lesions treated and 90% of women with invasive cervical cancer appropriately managed

However, administering the vaccine and ensuring the completion of the full vaccination series, which typically consists of two or three doses, remains challenging, particularly in countries where logistical barriers and limitations in healthcare infrastructure can hinder vaccine delivery. As a result, researchers have continued to explore alternative strategies, including the effectiveness of a single-dose regimen, to help overcome some of these obstacles.

Beyond Cervical Cancer

For many years, HPV vaccination has been largely viewed as a measure to protect girls and women from cervical cancer. However, over time, evidence has shown that HPV is linked to a broader range of malignancies, including cancers of the anus, vulva, vagina, penis, and oropharynx.

This growing understanding has shifted the focus toward gender-neutral vaccination strategies, recognizing that reducing the burden of HPV-related disease requires vaccinating both men and women to help limit transmission of the virus within the population.

Many countries that initially limited HPV vaccination to girls have since expanded their programs to include boys by adopting a gender-neutral approach.

Speaking with Univadis Italy, part of the Medscape Professional Network, Martino Barretta, MD, coordinator of the Vaccines and Immunizations Division of the Italian Federation of Primary Care Pediatricians in Italy, noted that although the message of “gender-neutral” HPV vaccination has gained traction in recent years, it cannot yet be considered fully established in Italy. He explained that many families still associate HPV exclusively with cervical cancer and, therefore, view it as a problem affecting only girls. “This is a very important cultural shift: we must move beyond the idea of a gynecological vaccination and consider the HPV vaccine a truly universal cancer prevention vaccine,” he said.

Coverage Gaps

In Italy, vaccination is recommended and provided free of charge to boys and girls during their 12th year of life.

The recommended schedule consists of two doses administered 6 months apart for individuals vaccinated before the age of 15 years and three doses administered at 0, 2, and 6 months for those vaccinated at the age of 15 years or older.

Catch-up vaccination programs are also available for older individuals who have not completed vaccination, extending to 26 years for women and 18 years for men.

“In Italy, vaccination coverage remains uneven across the various regions and falls short of the targets set by the Italy’s current National Vaccine Prevention Plan and the WHO,” Barretta said. He noted that regional disparities and gaps in the completion of the vaccination series, particularly among males, remain key challenges.

Data from the Italian Ministry of Health through December 31, 2024, illustrate these gaps:

• Complete vaccination coverage in the 2012 birth cohort was 51.18% for girls and 44.65% for boys.
• Among girls born in 2009, who represented the WHO monitoring cohort at the age of 15 years, coverage reached 70.58%.
• No Italian region has achieved the optimal 95% coverage threshold for any birth cohort.

These findings highlight the need for targeted catch-up initiatives and effective public communication strategies.

Addressing Hesitancy and Prevention

Persistent concerns and misconceptions continue to influence the vaccination decisions of adolescents and their parents.

According to Barretta, the most common concerns are related to vaccine safety and are often fueled by inaccurate or alarmist content circulating on social media.

Frequently cited fears include alleged effects on fertility and concerns about autoimmune diseases, such as type 1 diabetes.

“These concerns have no scientific basis,” Barretta said. “Evidence accumulated from more than 500 million doses administered worldwide over 20 years confirms the vaccine’s excellent safety profile.”

Another challenge is that the benefits of vaccination are not immediately apparent. Vaccination prevents diseases that may not develop until many years after infection, making the value of prevention less tangible for adolescents and their families.

Barretta emphasized the key role of pediatricians and other healthcare professionals in addressing these concerns.

“Providing clear information grounded in scientific evidence and communicated with empathy remains the most effective way to address vaccine hesitancy and misinformation,” he said.

“When pediatricians address the issue early, openly, and confidently, without embarrassment or an overly clinical approach, vaccination uptake can improve significantly,” Barretta said.

Barretta also highlighted a critical gap that can emerge when adolescents transition from pediatric care to adult primary care.

During this period, many adolescents and young adults stop attending routine preventive visits, increasing the likelihood that the recommended vaccinations will be missed.

“Collaboration between family pediatricians and primary care physicians has improved over time, but it still varies considerably across regions,” he said.

More standardized tools and coordinated approaches are needed to ensure the continuity of preventive care nationwide.

“The goal should be to create a seamless pathway in which young individuals continue to view prevention as a normal part of healthcare even after they leave pediatric care,” Barretta said.

Barretta reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.