Human papillomavirus is not an exceptional infection. It is the most common viral infection of the reproductive tract worldwide, and the vast majority of sexually active individuals will acquire at least one HPV genotype at some point in their lives. Most infections resolve spontaneously, without symptoms, without intervention, and without consequence. The clinical problem is the subset that does not resolve, and the cancers that follow.

Understanding HPV: Virology and Disease Burden

The Papillomaviridae family contains over 200 characterized genotypes, categorized into low-risk and high-risk groups based on their oncogenic potential. Low-risk genotypes, primarily HPV 6 and 11, cause approximately 90% of all anogenital warts. High-risk mucosal genotypes, including HPV 16, 18, 31, 33, 45, 52, and 58, are established carcinogens. Persistent infection with these genotypes leads to the expression of the viral oncoproteins E6 and E7, which promote degradation of the cellular tumor suppressors p53 and retinoblastoma protein (pRb). This molecular disruption bypasses cell-cycle checkpoints, impairs DNA repair pathways, and induces progressive genomic instability, ultimately driving invasive malignancy.

The epidemiological burden across Europe is substantial. According to the HPV Information Centre’s 2023 European Summary Report, approximately 58,169 women are diagnosed with cervical cancer annually across Europe, and 25,989 die from the disease. In Belgium specifically, the crude incidence rate is 10.9 per 100,000 women, resulting in approximately 639 new cases and 236 deaths each year, equivalent to a new diagnosis every day and a death every second day.

In the Belgian female population, HPV prevalence follows a bimodal distribution. High-risk HPV prevalence peaks sharply in women under the age of 25 to 30, reflecting the onset of sexual activity. Unusually, however, Belgium and France share a distinct epidemiological pattern: a sustained plateau of high-risk HPV prevalence of approximately 12% is observed in women aged 35 and older, indicating a substantial cohort with persistent, long-term infections. This has direct implications for catch-up vaccination strategy.

HPV Is Not Only a Women’s Issue

This is one of the most persistent and consequential misconceptions surrounding HPV.

Persistent high-risk HPV infection drives oncogenesis across multiple anatomical sites in both women and men. Cervical cancer accounts for the majority of HPV-attributable disease in women, but HPV is also responsible for cancers of the vagina, vulva, anus, penis, and oropharynx, the back of the throat, tonsils, and base of the tongue.

According to the HPV Information Centre’s Belgium-specific data, the crude incidence of oropharyngeal cancer in Belgium is 6.67 per 100,000 in men and 2.21 per 100,000 in women, a significant gender disparity that reflects the disproportionate burden of HPV-related head and neck cancer in males. In Europe overall, approximately 14,098 head and neck cancer cases in men annually are directly attributable to HPV. The incidence of HPV-driven oropharyngeal squamous cell carcinoma has risen significantly over recent decades across the continent.

Crucially, unlike traditional head and neck cancers caused by tobacco and alcohol, HPV-associated oropharyngeal cancer is molecularly distinct, demonstrating higher sensitivity to radiation and chemotherapy and a generally better prognosis. But it remains a cancer that is, in large part, vaccine-preventable.

For anal cancer, European data show that 88% to 97% of all cases are HPV-attributable, with HPV 16 and 18 present in 78% of cases. In Belgium, the crude incidence is 2.63 per 100,000 in women and 1.36 per 100,000 in men, with particularly high disease burden among immunocompromised individuals and men who have sex with men.

The Vaccine: Coverage, Efficacy, and Real-World Impact

The standard vaccine used in Belgium is Gardasil 9, a 9-valent recombinant vaccine targeting HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It is a prophylactic vaccine, meaning it prevents infection with these types and the diseases that follow. It does not treat existing infections.

A comprehensive Belgian study evaluating 255 histologically confirmed cervical cancer patients found that 92.9% were HPV-positive. Among these, HPV 16 was identified in 68.7% of cases, HPV 18 in 12.3%, HPV 31 in 6.2%, HPV 33 in 5.3%, and HPV 45 in 1.8%. While the first-generation bivalent and quadrivalent vaccines protect against approximately 81.1% of Belgian cervical cancers, the 9-valent vaccine, by targeting five additional high-risk types, provides coverage for over 90% of all invasive cervical cancers in the country.

Clinical trial evidence is now extensive. A systematic Cochrane review published in November 2025, evaluating 60 randomised controlled trials involving 157,414 participants, confirmed that all pre-qualified HPV vaccines are highly effective at preventing the infections and pre-cancerous lesions that lead to invasive disease. For young women aged 15 to 25 who were baseline-negative for high-risk HPV, vaccination reduced the risk of developing cervical intraepithelial neoplasia grade 2 or higher (CIN2+) by 60% for vaccine-matched HPV genotypes. Vaccination also reduced the need for local surgical treatments for cervical pre-cancer, conization or LEEP, by 24%, directly lowering the risk of subsequent obstetric complications including preterm birth.

Real-world data from national registries confirm what trials predicted. The English Registry Cohort (Falcaro et al., BMJ 2021/2024), analysing data from England’s national cancer registry, demonstrated that the bivalent vaccine program introduced in 2008 achieved an 83.9% to 87% reduction in cervical cancer incidence and a 94.3% to 97% reduction in CIN3 among girls routinely vaccinated at ages 12 to 13 years. The study concluded that the immunisation program has nearly eliminated cervical cancer in women born after September 1, 1995.

The Swedish Registry Cohort (Lei et al., New England Journal of Medicine, 2020), following 1.67 million girls and women aged 10 to 30 years from 2006 to 2017, found that quadrivalent vaccination was associated with an 88% reduction in the risk of invasive cervical cancer in girls vaccinated before the age of 17. Women vaccinated between the ages of 17 and 30 showed a smaller but still significant 53% reduction. A 15-year follow-up confirmed that this protection remains stable without any signs of waning immunity.

The second Cochrane review from November 2025, synthesising data from 225 studies involving more than 132 million people, showed that girls vaccinated at or before the age of 16 were 80% less likely to develop cervical cancer compared to unvaccinated girls.

Who Should Be Vaccinated and When

Timing is the single most important factor in vaccine effectiveness. The optimal time for HPV immunisation is prior to an individual’s sexual debut, before potential exposure to vaccine-targeted HPV types. Vaccination at a younger age is consistently associated with greater reductions in cervical cancer incidence than later vaccination. None of the available HPV vaccines have any therapeutic effect on pre-existing infections.

In Belgium, the current vaccination framework is as follows:

Routine HPV vaccination is offered free of charge through community-administered school programs. In the Flemish Community, the program targets students in the first year of secondary school, typically around age 12, using Gardasil 9 administered through the Centres for Pupil Guidance (CLB). In the French Community, covering Brussels and Wallonia, the program targets students in the second year of secondary school, ages 13 to 14. School-based coverage in Flanders has historically exceeded 90%, while coverage in Brussels and Wallonia has been considerably lower, partly due to approximately 30.6% of school health services in the French Community being classified as non-vaccinating centres.

For those who missed the routine adolescent programme, a significant policy shift took effect on June 1, 2026. Federal Health Minister Frank Vandenbroucke introduced outpatient reimbursement for Gardasil 9 extended up to the age of 30. Any unvaccinated young adult aged 19 to 30 can now obtain the vaccine with a co-payment of €12.80 per dose, or €8.00 for patients with increased allowance status. For high-risk groups, including people living with HIV, pre-transplant candidates, and stem cell or organ transplant recipients, this reimbursement extends up to the age of 45.

For adults over 45, vaccination is not routinely recommended, but individual clinical assessment remains appropriate for patients with specific risk profiles.

Dosing Schedule in Belgium

Belgium follows the European Medicines Agency (EMA) multi-dose standards, which differ from the more recently adopted single-dose approach in some other countries.

For initiation before age 15: a 2-dose schedule, with the second dose administered 6 months after the first. If the interval between doses is less than 6 months, a third dose is required. For initiation at age 15 or older: a standard 3-dose schedule administered at 0, 1 to 2, and 6 months. For immunocompromised individuals, including people living with HIV: a minimum of 2 doses, ideally 3 doses, regardless of age.

The WHO updated its position paper in December 2022 to permit simplified single-dose or two-dose schedules globally to improve access, noting that clinical trial data show a single dose provides comparable antibody persistence up to 10 to 11 years post-vaccination. However, Belgium maintains the multi-dose standard to ensure long-term, high-titre antibody response.

Vaccine Safety: What the Evidence Shows

The safety profile of HPV vaccines is well-established and has been evaluated across decades of clinical trial data and post-licensure surveillance.

The systematic Cochrane review of 60 trials, involving 97,272 participants in the safety analysis, showed no statistically significant difference in the incidence of serious adverse events between vaccine and placebo control groups. The most common reactions are mild, local, and transient, pain, erythema, or swelling at the injection site. Systemic events such as low-grade fever, mild fatigue, or headache occur at rates comparable to other standard adolescent vaccines.

Large-scale, registry-based cohort studies have systematically examined and disproven claims linking HPV vaccination to a range of chronic syndromes, including Postural Orthostatic Tachycardia Syndrome (POTS), Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), Complex Regional Pain Syndrome (CRPS), Guillain-Barré Syndrome, and Premature Ovarian Failure. Epidemiological evaluations have confirmed that the vaccine does not impair female or male fertility.

It is worth stating plainly: persistent HPV infections can lead to cervical cancers requiring surgical interventions, chemotherapy, or pelvic radiation, all of which are established causes of subsequent infertility. The vaccine does not cause infertility. Untreated HPV-related disease can.

Vaccination Does Not Replace Cervical Screening

This point requires emphasis. Vaccination and screening are complementary strategies, not alternatives.

While the 9-valent vaccine covers approximately 90% of cervical cancer cases, the remaining 10% are caused by high-risk HPV types not covered by the vaccine. Adults receiving catch-up vaccination may have been exposed to high-risk HPV types prior to immunisation. Because the vaccine is strictly prophylactic and has no therapeutic effect on established infections, these individuals remain at risk for dysplastic progression.

A Note From the Clinic

At Nexxmedis, we offer the full spectrum of HPV-related prevention and diagnosis, colposcopy using the Dysis Computer-Aided System with cervical mapping, cervical screening aligned with Belgium’s updated 2025 HPV DNA protocol, and consultations for patients who are uncertain about their vaccination status or screening history.

This article has been written for informational purposes and reflects current scientific evidence and Belgian clinical guidelines as of June 2026. It does not constitute medical advice. All medical decisions should be made in consultation with a qualified healthcare professional.

Sources & References

• UpToDate: Human Papillomavirus Vaccination (2026)
• Cochrane Library: HPV vaccination for the prevention of cervical cancer, meta-analysis of 60 RCTs (2025)
• World Health Organization: HPV Vaccination and the Risk of Invasive Cervical Cancer, Swedish Registry (2020)
• World Health Organization: HPV Vaccines Position Paper, Updated Dosing Recommendations (2022)
• HPV Information Centre: Human Papillomavirus and Related Diseases, Belgium Report (2023)