The economic burden of HPVrelated diseases: Belgium
Key highlights
• Human Papillomavirus (HPV) infection remains one of the most prevalent sexually transmitted infections, affecting millions of individuals each year.
• In Belgium, where the median age at first sexual intercourse ranges from 18.0–20.9 years for women and 17.4–20.4 years for men, meaning that most individuals aged 17 and older, totalling over 80% of the population, are at risk of HPV infection and related diseases due to sexual activity.
• Cervical cancer (CC) is the 4th most frequent cancer among women between 15 and 44 years of age in Belgium.
• In total, approximately 1,212 and 385 HPV-associated cancer cases and deaths, respectively, occur annually in Belgium.
• Considering the 18,000 new cases of genital warts in Belgium annually, total treatment costs are estimated at €6.7 million per year.
• The most costly CIN treatment was associated with cervical intraepithelial neoplasia (CIN) 3 (€928.3), followed by CIN2 (€733.8), and CIN1 (€407.3).
• Penile cancer showed the highest cost in the distant stage (€43,184), followed by vulvar cancer (€42,844). In contrast, vaginal cancer has the lowest costs in the distant stage (€38,892).
• Based on current data, indirect productivity loss costs from premature death due to CC were estimated at €68 million per year.
• The total indirect economic burden of HPV-related cancers, including CC, is about €111 million.
• Considering the most recent incidence of CC (2020) and indirect costs, the total average annual economic burden for all CC cases is approximately €80.3 million, which is the highest of all types of HPV-related cancers.
• The total average annual economic burden for all other HPV-related cancers is approximately €60.6 million.
• Total treatment costs of CIN2+ were estimated at €7.3 million, excluding CIN1 and associated treatment costs. This could increase the total burden even more.
• The overall economic burden of HPV-related diseases in Belgium was estimated at €154.9 million, highlighting the significant financial impact of the virus and associated diseases.
• As the World Health Organization (WHO) sets out that national CC screening coverage should reach 70% by 2030, screening coverage in the Flemish region, Walloon region, and Brussels Capital region is suboptimal at a rate of 63.7%, 48.2%, and 46.3%, respectively.
• The most common reasons for not attending a screening programme are lack of awareness or information, cultural or language barriers, poor access to
healthcare services (e.g. inconvenient location or appointment times), and discomfort, fear, or embarrassment as a response to the test.
• As of January 2025, the recommended CC screening has shifted from a 3-yearly cytological examination to a primary HPV test, conducted every five years, for women aged 30-64.
• Considering the WHO target of 90% of girls being fully vaccination with a HPV vaccine by the age of 15, vaccination coverage in the Wallonia-Brussels region is suboptimal (55.1% for girls and 49.5% for boys in 2022-2023). Vaccine uptake in the Flemish region is approximately 90%.
• Since 2019, vaccination of boys, with the 9vHPV vaccine, has been implemented as part of the gender-neutral HPV vaccination (GNV) programme in both the Flemish and Wallonia-Brussels region.
• GNV with the 9vHPV vaccine significantly reduces HPV-related disease incidence, deaths, and healthcare costs compared to female-only vaccination FOV with either the 9vHPV or 2vHPV vaccines in Belgium.
• While initial investments in widespread vaccination and screening programs are substantial, the long-term savings from decreased cancer incidence and the potential for less frequent screening could offset these costs.
3.2.1
3.2.1.1.
3.2.1.2.
Abbreviations
Abbreviation Definition
2vHPV
4vHPV
9vHPV
CC
CCD
CIN
ECDC
FIGO
FOV
GNV
GP
HCPP
HPV
IARC
ICER
KCE
QALY
SHS
SP
WHO
2-valent human papillomavirus vaccine
4-valent human papillomavirus vaccine
9-valent human papillomavirus vaccine
Cervical cancer
Centre for Cancer Detection
Cervical intraepithelial neoplasia
European Centre for Disease Prevention and Control
International Federation of Gynecology and Obstetrics
Female-only vaccination
Gender-neutral vaccination
General practitioner
Healthcare payer perspective
Human Papillomavirus
International Agency for Research on Cancer
Incremental cost-effectiveness ratio
Belgian Health Care Knowledge Centre
Quality-adjusted life year
School health services
Societal perspective
World Health Organization
1. Introduction
Globally, Human Papillomavirus (HPV) infection remains one of the most prevalent sexually transmitted infections, affecting millions of individuals each year. In Belgium, as in many other countries, HPV poses a significant threat to public health due to its association with various cancers, including cervical, anal, and oropharyngeal cancers, as well as other conditions such as genital warts. These diseases impact individual health and well-being while imposing substantial socioeconomic burdens on healthcare systems and society at large.
The socioeconomic implications of HPV-related diseases in Belgium, as elsewhere, are multifaceted. Direct medical costs related to diagnosing, treating, and managing HPVassociated cancers represent a significant economic burden on the healthcare system. Furthermore, indirect costs such as productivity losses due to morbidity, and premature mortality amplify the economic impact, underscoring the importance of effective prevention strategies. These include widespread vaccination programs and robust screeninginitiatives aimed atearlydetectionandinterventiontomitigatebothhealthand financial consequences.
Investigating the socioeconomic aspects of preventive measures against the virus is imperative for accurately allocating resources to mitigate the health and financial burden caused by HPV-related diseases. Vaccination against high-risk HPV types has proven highly effective in reducing infections and the subsequent development of HPVassociated cancers. Meanwhile, early screening programs, particularly for cervical cancer (CC), play a crucial role in identifying precancerous lesions before they progress to invasive disease. However, challenges remain in achieving widespread screening and addressing disparities in vaccination coverage across different regions and populations in Belgium. Assessing the cost-effectiveness and socioeconomic impact of these preventive measures is essential for guiding resource allocation and shaping public health policies to mitigate the health burden of HPV-related diseases while alleviating their economic burden.
This report aims to provide a comprehensive analysis of HPV and its associated diseases within the Belgian context, focusing on their socioeconomic impact and the effectiveness of current preventive measures. By exploring these facets, it aims to provide insights into the current landscape, identify gaps in knowledge, and offer recommendations to enhance public health outcomes and economic efficiency in managing HPV infections and associated conditions in Belgium.
2. Methodology
To achieve this, we conducted a targeted literature review with a specific emphasis on Belgium. Using PubMed, we identified indexed literature and complemented this with grey literature sources to gather additional relevant sources of information. For the PubMed search, key terms such as“health care costs,”“costs,”“cost-effectiveness,”and “cost of illness,” combined with HPV-related terms, were applied to screen and identify relevant articles. Our review included studies addressing the economic impact of HPVrelated diseases in Belgium as well as those evaluating the economic effects of preventive measures. Moreover, a targeted Google search was conducted to identify any additional relevant information, prioritizing credible sources such as governmental and public health websites. The identified articles and documents were then reviewed to extract relevant data specific to Belgium, focusing on the costs associated with HPVrelated diseases. This included direct medical costs, indirect costs, and broader economic impacts. This methodology ensures a comprehensive overview of the economic burden of HPV-related diseases in Belgium by integrating both peerreviewed studies and reliable grey literature.
3. The Belgian Landscape
Statistics for Belgium
Population (2023) and regions (1)
11.8 million divided over Flemish region, Walloon region, and Brussels Capital region (Wallonia-Brussels
Currency and GDP per capita (2023) (2) Euro, (EUR, €); €63,698 (USD 72,070)
Community government HPV programs (3-5)
Vaccination
• Flemish region (♀, 2010; ♂, 2019)
• Wallonia-Brussels (♀, 2011; ♂ 2019)
Cervical cancer screening
• Flemish region
o Citology, 3-yearly, women aged 25-64 (2013)
o Primary HPV testing, 5-yearly, women aged 30-64 (2025)
• Wallonia-Brussels
o Primary HPV testing, 5-yearly, women aged 30-64 (2025)
Vaccine coverage (two doses) (5-8)
• National: 70% ♀ (2021); 64% ♂ (2021)
• Flemish region: 91% ♀ ♂ (2021)
• Wallonia-Brussels: 55.1% ♀ (2022-2023); 49.5% ♂ (2022–2023)
Figure 1. Map of Belgium and key statistical information for the country
3.1 HPV transmission and HPV-related diseases in Belgium
HPV is spread through sexual and oral contact, i.e. through contact with infected genital skin, mucous membranes, and bodily fluids (9). Sexually active individuals will acquire one or more HPV infections at least once in their lifetime, without necessarily experiencing symptoms or developing any pathologies as these infections usually clear spontaneously within a few years (9-11). In Belgium, the range of median age at first sexual intercourse for women and men is 18.0–20.9 and 17.4–20.4 years of age, respectively (12). As all sexually active individuals are at risk of HPV infection and given that over 80% of the Belgian population is aged 17 and older, a considerable part of the Belgian population is at risk of HPV infection and associated HPV-related diseases (11, 13).
CCis one of the prevalentHPV-related diseases. In Belgium, it ranks as the fourth most frequent cancer among women between 15 and 44 years of age (9, 14). With a crude incidence rate of approximately 10.9 cases per 100,000 women per year, current estimates indicate that every year about 639 women of all ages are diagnosed with CC in Belgium (estimates for 2020) (5, 14). This corresponds to about 61 cases in the Brussels Capital region, 229 cases in the Walloon region, and 349 cases in the Flemish region on an annual basis (14). Moreover, it ranks as the 16th leading cause of female cancer deaths in Belgium, with a crude mortality rate of 4.04 deaths per 100,000 women per year, leading to about 236 deaths each year (estimates for 2020) (5).
Other HPV-related cancers in Belgium include cancers of the vagina, vulva, anus, penis, oral cavity, oropharynx, and laryngeal, which may result from an infection with a high-risk HPV types 16 and 18 (9). After CC, oral cavity cancer is the second most frequent HPV-related cancer, with a crude incidence rate of 6.02 cases per 100,000 for females and 11.1 cases per 100,000 for males (estimates for 2020) (12). It is important to note that, unlike CC, not all cases of the other cancers are directly associated with HPV (15). A summary of the annual number of cases and deaths, the estimated percentage of HPV attribution for HPV-related cancers, and the total number of HPVattributable cases and deaths is presented in Table 1.
Table 1. Estimated annual number of new cases, deaths, and total number of HPV-related cancer cases in Belgium in 2020
Oral Cavity Cancer M: 640, W: 352 M: 202, W: 109 2.2%
Laryngeal Cancer M: 517, W: 100 M: 159, W: 30 2.4%
Abbreviations: HPV, Human Papilloma Virus; M, men; W, women.
aTotal number of HPV-attributable cases and deaths was calculated by multiplying the annual number of cases/deaths by HPV attribution
The total number of HPV-related cancer cases can be estimated based on the annual number of cases multiplied by the HPV attribution percentage for each cancer type. Consequently, approximately 1,212 and 385 HPV-related cancer cases and deaths, respectively, occur annually in Belgium.
HPV-related diseases also include cervical intraepithelial neoplasia (CIN), which is a precursor to CC. CIN refers to precancerous lesions or abnormal growth of cells observed in the cervix (5, 16). It is diagnosed by analysing cervical tissue obtained through a biopsy or surgical excision, often detected during routine screening to prevent progression to invasive cancer (5). The condition is classified into three grades: CIN1, CIN2, or CIN3, based on the degree of abnormal cell growth and thickness of the layer of the cervix (5). Specific data on the prevalence of CIN1, CIN2, and CIN3 in Belgium are limited. Based on the number of new annual precancerous lesions in Europe and Belgium’s share of the European population, between 10,000 to 20,000 new cases of CIN2+ (CIN2 and CIN3) would occur annually (17). Additionally, data from the International Agency for Research on Cancer (IARC) demonstrated the burden of HPV infection as the prevalence of high-risk types HPV-16 and 18 among women with CIN (5). In this context, HPV 16 and 18 prevalence in women with low-grade cervical lesions (CIN1) is 26.4%, while the prevalence is 51.8% among women with high-grade cervical lesions (CIN2 and CIN3) (5).
Additionally, HPV is related to non-cancerous diseases such as genital warts. Infection with low-risk HPV types, in particular HPV-6 and 11, can lead to the development of genital warts (9, 18). Based on the number of new annual cases attributable to HPV-6 and 11 in Europe and Belgium’s share of the European population, about 18,000 new cases of genital warts occur annually in Belgium (17).
3.2 Socioeconomic burden of HPV-related diseases in Belgium
HPV-related diseases not only contribute to increased mortality but also place a substantial financial burden on individuals and society. To assess this socioeconomic impact, we analysed data sourced from the literature. This involved extracting reported healthcare costs incurred by both the healthcare system and patients for each HPVrelated condition. Additionally, whenever available, we included societal costs, such as productivity losses due to absenteeism or mortality, informal care expenses, and productivity losses associated with caregiving.
3.2.1 Healthcare costs
3.2.1.1. Cervical intraepithelial neoplasia (CIN) and cervical cancer
Data on the economic burden of HPV-related diseases in Belgium is, in general, limited. One frequently referenced study by Annemans et al. 2008 aimed to estimate the economic burden of CC and CIN in Belgium from both the public healthcare payer perspective (HCPP) and societal perspective (SP) (16). The HCPP included direct medical costs (i.e. hospital, procedures, and physician visit costs) reimbursed by the healthcare payer, while the SP included all direct medical patient costs and productivityrelated (indirect) costs. Considering the CC managing costs, the total annual hospital cost was calculated by summing all costs incurred for all hospital admissions within the calendar year. Ambulatory costs were not considered, but productivity losses have been estimated (Section 3.2.2.). Considering the annual cases observed in 2020, the annual cost of CC treatment for the Belgian population was estimated to be approximately €9.5 million, with an average yearly hospital cost of approximately €14,820 for a CC patient, adjusted for 2025 inflation. Importantly, patients classified with a higher International Federation of Gynecology and Obstetric (FIGO) stage were associated with higher annual costs, ranging from €8,141–€12,774 for FIGO stage I, €8,325–€17,557 for FIGO stage II and III, and €20,544–€35,498, adjusted for 2025 inflation When considering additional costs beyond hospital-based treatments for the number of cases observed in 2020, the total annual cost of CC was estimated at €14.79 million
(SP), adjusted for 2025 inflation. Given Belgium's population of around 11.8 million people, the cost of CC treatment, while substantial, is spread across the population. Notably, this becomes more significant when considered within the broader context of national healthcare expenditure. The total burden on the healthcare system and society is much greater when factoring in the long-term costs of ongoing treatment and the potential economic impact on patients, such as lost productivity.
CIN managing costs were estimated based on the proportion of hospital-based interventions multiplied by resource use with the mean cost per treatment procedure. Consequently, the most costly treatment was associated with CIN3 (HCPP €570.6, SP €928.3), followed by CIN2 (HCPP €442.0, SP €733.8), and CIN1 (HCPP €331.9, SP €407.3), adjusted for 2025 inflation. Based on a survey to collect information on the management of HPV-related diseases by physicians, 19% of CIN1 patients were given treatment, compared with an expected higher proportion of treated CIN2 and CIN3 patients (77% and 93%, respectively). Considering these percentages and the mean cost estimates for CIN treatment, the estimated total cost of CIN management in Belgium was estimated at €258,315 (HCPP) and €316,574 (SP) for CIN1, €1.1 million (HCPP) and €1.8 million (SP) for CIN2, and €1.7 million (HCPP) and €2.8 million (SP) for CIN3, adjusted for 2025 inflation. These findings underscore the importance of early detection and intervention strategies, particularly for higher-grade CIN lesions, to manage healthcare costs effectively while providing necessary care to patients. Table 2 shows shows the costs per episode of care for CIN.
Based on the real-world data from the IMS Health Belgian Hospital Disease Database, costs per episode of care, defined as the cost of management from diagnosis to resolution of the case, for CC and CIN were reported (4). Table 2 shows the costs per episode of care for CC and CIN, with distant CC and CIN3 having the highest costs per episode. These numbers are broadly aligned with the study of Annemans et al. 2008 Differences in the results can be explained by the distinct methodologies used in each article, such as slightly different classification scales, varying calculatios, inflation assumptions, and data sources.
Cervical intraepithelial neoplasia
- Grade 1 intraepithelial neoplasia
- Grade 2 intraepithelial neoplasia
- Grade 3 intraepithelial neoplasia
Cervical cancer
- Locala 14,509
- Regionala
- Distanta
aDisease stages can be related to traditional Tumor-Node-Metastasis (TNM) classification system as follows: ‘Local disease’ corresponds to stages I and II TNM classification (localized primary tumor); ‘Regional disease’ corresponds to stage III TNM classification system (metastasis to regional lymph nodes); ‘Distant disease’ corresponds to stage IV TNM classification system (distant metastatic disease).
Taking into account the minimum estimated number of new annual CIN2+ cases, reported in the previous section on CIN incidence, and the cost per episode for CIN2, the total treatment costs of CIN2+ were estimated at €7.3 million. This estimate is higher than the one reported in the study by Annemans et al. (2008) (16) Differences in results can be attributed to variations in incidence data, differences in cost assumptions, methodological approaches, calculation models, and inflation assumptions
3.2.1.2. Other HPV-related cancers and diseases
Although the association between HPV and other HPV-related diseases is not as definitive as the 100% association between HPV and CC, these diseases also contribute significantly to the overall healthcare and associated costs. Costs per episode of care for HPV-related cancers other than CC were alsoreportedand adjustedfor 2025 inflation in the following section (4, 19). For instance, penile cancer showed the highest cost in the distant stage (€43,184), followed by vulvar cancer (€42,844) (Table 3). In contrast, vaginal cancer has the lowest costs in the distant stage (€38,892). This may indicate differences in treatment protocols, available therapies, or associated complications among cancer types.
Regional-stage costs are consistently higher than local-stage costs and, in some cases (e.g., anal cancer), even surpass distant-stage costs. This highlights the resourceintensive nature of managing cancer that has spread regionally, often requiring complex surgeries, radiation, and chemotherapy. For anal cancer, distant-stage treatment costs (€25,642 for females, €30,334 for males) are lower than regional-stage treatment costs (€43,173 for females, €43,378 for males) (Table 3). This is an exception to the observed Disease
Economic burden HPV-related diseases (BEL)
Table 2. Costs per episode for cervical intraepithelial neoplasia and cervical cancer, adjusted to 2025 inflation (4)
trend, suggesting that treatments for distant-stage anal cancer may differ significantly or involve fewer intensive interventions compared to regional-stage treatment.
For most HPV-related cancers, the sharp increase in costs at more advanced stages underlines the importance of early detection and prevention to reduce the economic burden of these cancers.
Vaginal cancer
Vulvar cancer
- Locala
Penile cancer
- Locala 23,044
- Regionala
- Distanta
Anal cancer
- Locala
W: 29,267, M: 24,888
- Regionala W: 43,173, M: 43,378
- Distanta W: 25,642, M: 30,334
Head and neck cancerb
- Locala
W: 20,609, M: 25,366
- Regionala W: 33,243, M: 32,198
- Distanta W: 26,332, M: 35,621
Abbreviations: M, men; W, women.
aDisease stages can be related to traditional Tumor-Node-Metastasis (TNM) classification system as follows: ‘Local disease’ corresponds to stages I and II TNM classification (localized primary tumour); ‘Regional disease’ corresponds to stage III TNM classification system (metastasis to regional lymph nodes); ‘Distant disease’ corresponds to stage IV TNM classification system (distant metastatic disease).
bHead and neck cancers include oral cavity, oropharyngeal, and laryngeal cancers.
Moreover, the total mean costs of genital warts management, including ambulatory and hospital costs, were estimated at €319.1 (HCPP) and €371.7 (SP) per female patient and €314.2 (HCPP) and €367.9 (SP) per male patient, adjusted for 2025 inflation (16).
Considering the 18.000 annual genital warts cases in Belgium, the total treatment costs of genital warts were estimated at €6.7 million, adjusted to 2025 inflation (17). This underscores the collective financial burden of managing this condition and emphasises the importance of preventive strategies. Disease
Economic burden HPV-related diseases (BEL)
Table 3. Costs per episode for HPV-related cancers, adjusted to 2025 inflation (4, 19)
3.2.2 Indirect costs
Reported indirect costs associated with HPV-related diseases are scarce in the literature on Belgium. However, these costs can be substantial, particularly in the case of cancer, and consist primarily of productivity losses. These arise from absenteeism due to cancer treatment, premature death, and the caregiving responsibilities by family members or other caregivers. Additionally, there are emotional and psychological impacts on patients and their families, which may contribute to increased mental healthcare costs.
Only one estimation of indirect costs related to CC was reported in the literature. The study by Annemans et al. (2008) reported productivity loss and related costs due to the cancer (16). Considering the annual incidence of CC in Belgium, a mean cost of €206,25 per workday lost (adjusted for 2025 inflation), and that women diagnosed with CC stop working for an average of 120 days, they estimated total productivityrelated losses at €5.1 million (adjusted for 2025 inflation). This underscores how diseases like CC affect not only healthcare systems but also the broader economy through lost labour contributions.
A rough estimation of indirect productivity losses arising from premature death to CC was derived by calculating the economic impact of premature mortality, considering life annual cases and deaths, life expectancy, years lost, employment rates, and average annual salaries (Table 4).
4. Estimated indirect productivity losses arising from premature death to CC based on most recent data
Parameters
Values
Annual number of cases (2020) (5) 639 cases
Annual number of deaths (2020) (5) 236 cases
Average age of HPV-related death (2018) (20) 59 years
Average age of retirement in Belgium 67 years
Average years of life lost due to CC 8 years
Total life years lost 1,888 yearsa
Average employment rate for women aged 30-65 in Belgium (2024) (21) 70%b
Average gross annual salary for women in Belgium (2020) (22, 23) €51,599c
aDerived from multiplying death cases by years of life lost.
bBased on available employment rate for women aged 50-64 in 2024 (61.29%) (21). Given that employment rates are generally higher among younger age groups, average employment rate for women aged 30-65 is estimated at approximately 70%.
Table
cDerived from provided internal document on salaries in Belgium.
dDerived from multiplying total life years lost by employment rate.
eDerived from multiplying employed life years lost by the average gross annual salary.
Based on current data and assuming a similar incidence for 2025, indirect productivity loss costs from premature death due to CC were estimated at €68 million. These estimates might be even higher when also considering short- and longterm work absence and caregiver absenteeism. Similarly, indirect productivity losses from premature death due to other HPV-related cancers could be estimated (Table 5). The same calculation as above is applicable, except for the annual number of deaths. For these cancers, the total number of HPV-related deaths is used, taking into account the different percentages of HPV attribution other than 100% for CC (Table 1).
Table 5. Estimated indirect productivity losses arising from premature death to HPV-related cancers based on most recent data
Based on this, total productivity losses for all HPV-related cancers, other then CC combined, were estimated at €43 million Altogether, the indirect economic burden of HPV-related cancers, including CC, is about €111 million.
Compared to the study by Annemans et al. 2008, the estimated productivity losses based on current data are much higher, as our estimation and the article address different components of the economic burden of CC. In the study by Annemans et al. 2008 a methodology from the French National Cancer Institute, tailored to Belgian data was used. Importantly, Belgian-specific dataonlostworkdays per case was not available and the calculation incorporates the Belgian female activity rate, which represents the proportion of women in the workforce. This lowers the productivity loss estimate since it excludes women who are unemployed or out of the labour force. The reliance on French data and a lack of Belgian-specific studies may lead to underestimations if the disease burden in Belgium is higher or work patterns differ. Also, a fixed daily wage is applied to lost workdays, rather than considering annual salaries or broader economic impacts. The methodology used for productivity losses in the article is more conservative,
focusing on immediate, short-term costs during treatment. In contrast, the estimation in this report includes lifetime earnings lost due to mortality, resulting in much higher estimates. This difference in scope and methodology explains the significant gap between the two estimates.
The lack of reported indirect costs means that the true socioeconomic burden of HPVrelated diseases in Belgium is likely underestimated. This can lead to insufficient resource allocation for prevention and treatment programs. Recognizing and addressing these hidden costs is crucial for a comprehensive understanding of the impact of HPVrelated diseases on individuals and society, ultimately guiding more effective public health policies and interventions.
3.2.3 Total costs
A rough estimation of the total average annual costs of various HPV-related cancers, including direct and indirect costs, is provided in Table 6. This estimation was derived by taking into account the annual incidences of cases in 2020, as well as the percentage attribution to HPV multiplied by the respective costs per episode which were reported in the previous section, plus total productivity losses.
Table 6 Estimated total annual costs per HPV-related cancers taking into account average costs per episode per incidence case, the number of these events, and the percentage of events attributable to HPV
aWeighted average of costs per episode of all cancer stages (for both females and males for anal and head and neck cancer), considering the stage distribution for each cancer type.
The total average annual economic
burden HPV-related diseases (BEL)
annual economic burden for all other HPV-related cancers is approximately €60.6 million. This corresponds to a total average annual economic burden of HPV-related cancers cases of approximately €140.9 million. Productivity losses contribute significantlyto the total cost, suggestingthat, beyondtreatment expenses, the economic impact of lost work, disability, and premature mortality is a major burden. Importantly, these estimations exclude other indirect societal costs, such as absenteeism, disabilityrelated costs, psychological distress, and reduced quality of life as there is no data available. These intangible costs could significantly increase the total burden, meaning the true economic impact is likely underestimated with these numbers.
Lastly, considering the 18.000 annual genital warts cases in Belgium, the total treatment costs of genital warts were estimated at €6.7 million, adjusted to 2025 inflation (17). This underscores the collective financial burden of managing this condition and emphasises the importance of preventive strategies. Altogether, a rough estimation of the overall economic burden of direct and indirect costs associated with CC, other HPV-related cancers, genital warts, and CIN can be made (Table 7).
Table 7. Estimation of the overall economic burden of direct and indirect costs associated with CC, other HPV-related cancers, genital warts, and CIN2+
So, the overall annual economic burden of HPV-related diseases in Belgium was estimated at €154.9 million, highlighting the significant financial impact of the virus and its associated diseases. Notably, this estimate does not include the costs associated with CIN1 lesions or indirect societal costs, meaning the actual burden is likely even higher. These expenses, which encompass direct medical costs and productivity losses, highlight the urgent need for enhanced prevention efforts. Expanding HPV vaccination programs, improving screening strategies, and increasing public awareness could significantly reduce both the economic strain and the long-term health consequences of HPV-related diseases.
3.3 Economic benefits of HPV-related preventive measures
To fight the occurrence of HPV-related diseases and reduce the socioeconomic burden associated with the virus, several preventive measures have been put in place
in Belgium. One of these preventive measures is screening, though, for years, it has not been centrally organised as a national CC screening programme (24). Instead, regional health authorities were responsible for determining screening ages, the primary screening test used, and the screening interval or frequency of screening and their approaches vary (5). As of 2013 in the Flemish region, women aged 25–64 were invited by the Centre for Cancer Detection (CCD) as part of a semi-organised CC screening programme every three years (5, 25). Cervical cytology, or a pap smear, was performed as the primary screening test (25). Women who did not have a sample taken in the last three years received a letter from the CCD to encourage them to have a smear taken by a general practitioner (GP) or gynaecologist (25). As the World Health Organization (WHO) sets out that national CC screening coverage should reach 70% by 2030, screening coverage in the Flemish region is suboptimal at a rate of 63.7% (26-28).
In the Walloon region and Brussels Capital region (Wallonia-Brussels region, French Community), screening coverage is even lower at a rate of 48.2% and 46.3%, respectively (27, 28). In addition, screening was more opportunistic in these regions as there is no (semi)-organised screening programme. For women aged 25–64, it is recommended to have a smear taken every three years, however, there is no active invitation like in Flanders (5) Importantly, in the Wallonia-Brussels region, there are several initiatives to raise awareness and improve participation in CC screening (29, 30). Despite these efforts, participation rates in CC screening remain suboptimal The most common reasons for not attending a screening programme are a lack of awareness or information, cultural or language barriers, poor access to healthcare services (e.g. inconvenient location or appointment times), and discomfort, fear, or embarrassment as a response to the test (25, 31, 32)
Considering these reasons for the lack of screening attendance, the WHO recommendation, and the regionally (semi)-organized screening, the Belgium government decided to switch to a national primary HPV testing for women aged 30–64 (24, 25, 33) As of January 2025, the recommended CC screening has shifted from a 3-yearly cytological examination to a primary HPV test, conducted every five years, for women aged 30–64 (33). The technique to obtain a sample is equal, however, HPV testing checks whether genetic material unique to HPV is present in cervical cells and is therefore easier to interpret as the test is either negative or positive (34). In contrast, cytological examinations require a pathologist to examine the cells and check for abnormal changes (34) Research showed that HPV testing is more sensitive, and thus can earlier detect cervical lesions earlier, making it more effective in reducing the number of future CC cases (25, 33, 35-38) Lastly, HPV testing reduces the testing frequency from three to five years. Based on the clinical guidance provided by several
cancer institutes and related researchers, Table 8 shows a summarized overview of the new CC testing scheme for different age groups in Belgium.
<25 years
25–29 years
Cytological examination
Every three years
If atypical cells are observed, HPV testing is performed and reimbursed
30–64 years HPV testing Every five years If HPV is detected, cytology is performed to confirm this.
Positive for HPV 16/18: direct colposcopy, regardless of cytology.
The risk of CC is almost nonexistent
HPV infections are common but often resolve spontaneously in this age group.
Primary HPV screening may cause false positives, leading to unnecessary tests and overtreatment.
In case of a positive result, additional cytology is performed
≥65 years
Cotesting (cytology + HPV) on the same sample
Once
Abbreviations: CC, cervical cancer; HPV, Human Papilloma Virus
Yes, as no test has been reimbursed in the previous ten years.
Cotesting is recommended in this cohort to maximize sensitivity
Another preventative measure to fight the occurrence of HPV is vaccination. In contrast to screening, vaccination strategy is still regulated on a regional level, except for federal level catch-up vaccination For the Flemish and Wallonia-Brussels regions, HPV immunization programs for females were initiated in 2010 and 2011, respectively (4) Specifically, in the Flemish region in 2010, the 4-valent HPV (4vHPV, targeting HPV 6/11/16/18) vaccine was made available in a 3-dose schedule for females in the first year of secondary school (11-12 years old) for free through school health services (SHS) (4, 39) These are services provided by healthcare workers to students enrolled in primary
Economic burden HPV-related diseases (BEL)
Table 8. New CC testing scheme for different age groups in Belgium (33)
or secondary school (6). In 2014, the 2vHPV vaccine (targeting HPV 16/18) was made available in a 2-dose schedule and in 2018, the 9vHPV vaccine (targeting HPV 6/11/16/18/31/33/45/52/58) replaced the 2vHPV vaccine (4). Additionally, since 2019, vaccination of boys, mainly with the 9vHPV vaccine, has been implemented as part of the gender-neutral HPV vaccination (GNV) programme (39). Overall, vaccine uptake in the Flemish region is approximately 90% (4, 40).
In the Wallonia-Brussels region in 2011, the 2vHPV vaccine was made available through free SHS for females in the second year of secondary school (13–14 years old) (4). Initially, this was in a 3-dose schedule and since 2014 in a 2-dose schedule (4, 39). Like the Flemish region, since 2019, vaccination of boys, mainly with the 9vHPV vaccine, has been implemented as part of the GNV HPV programme (4). Currently, for both regions, catch-up HPV vaccination for girls aged 12–18 who did not have access to vaccination through a regional program is available with national reimbursement (4). Importantly, compared to the Flemish region, vaccine uptake in the Wallonia-Brussels region is lower: 55.1% for girls and 49.5% for boys (4, 8, 39). Notably, only 68% of eligible girls are affiliated with an SHS offering HPV vaccination and in total, 71% of the SHSs propose this vaccination (41).
3.3.1 Cervical cancer screening
The evaluation of CC screening programs is essential. It is crucial to identify strategies that can successfully lower barriers to screening participation and ultimately improve coverage, accessibility, feasibility, and cost-effectiveness.
Before the recent switch to primary HPV testing, the budget impact on CC screening based on primary HPV testing with dual-stain cytology triage, instead of cytology screening, was assessed in Belgium (42). Dual-stain cytology, which detects the biomarkers p16 and Ki-67, enhances sensitivity by reducing false positives and identifying women at risk when HPV results are positive but cytology is inconclusive or negative (43). The results indicated that primary HPV testing with dual-stain cytology triage is superior and therefore, a most cost-effective strategy compared to primary cytology. The cost-effectiveness of an intervention is measured using the incremental cost-effectiveness ratio (ICER), which compares the additional cost of an intervention to the additional health benefits it provides. The ICER was negative for women aged 30–65 (−€506,537,037), adjusted for 2025 inflation. This means that the intervention not only provides better health outcomes but is also less expensive than the alternative, making it a highly cost-efficient option.
For women aged 30–65, the analysis showed a budget reduction of 22% for dual-stain cytology with annual cost savings of €6.5 million for the Belgian healthcare system, adjusted for 2025. Additionally, this screening approach is projected to decrease the incidence of CC by 30% in women aged 30–65 and reduce annual CC mortality by 30% in this age group, thereby improving women's health outcomes. While initial costs may rise due to the introduction of a new testing method, the long-term benefits, including decreased incidence and mortality rates, result in significant cost savings over time.
After years of cytological examinations and considering the recent switch to national primary HPV testing for women aged 30–64, the costs and potential benefits of co-testing (combining HPV testing with cytology) in Belgium were assessed (24, 25, 33). Two hypothetical algorithms for CC screening in Belgium were compared: HPV testing and co-testing. The results indicated that co-testing would detect more cervical precancer and reduce the risks of missing cases compared to HPV testing only. Specifically, co-testing would detect an additional 2,351 CIN2 and CIN3 cases per year compared to primary HPV testing. Moreover, considering a cost-neutral approach for pricing HPV testing and cytology, co-testing is less expensive than HPV testing. Importantly, co-testing becomes more expensive if the cost per HPV test and cytology are the same. This also comes at increased resource use as co-testing would require an additional 13,173 colposcopies, 67,731 HPV tests, and 477,020 cytological examinations Thus, while co-testing offers improved detection rates and potential cost advantages under certain pricing scenarios, its national implementation would place a heavier strain on healthcare infrastructure compared to HPV testing only.
Considering the suboptimal screening coverage rates in Belgium and the recommendation of the WHO (70% coverage), the study by Gezels et al. (2024) aims to evaluate whether offering self-sampling kits through GPs can improve CC screening participation among women aged 31–64 in the Flemish region (25) This study compares three different approaches: GPs offering kits during consultations, sending kits with personalized letters, or providing the standard invitation letter for a smear test By addressing barriers through GP involvement and self-testing, the study also includes a cost-effectiveness analysis tocompare costs perscreened womanacross interventions. Results, expected by March 2025, may confirm the potential of self-sampling kits to boost participation, enable earlier detection, and improve accessibility.
3.3.2 Vaccination
Several cost-effectiveness studies have shown that GNV vaccination with the 9vHPV for boys and girls aged 12 or older is cost-effective at a willingness-to-pay threshold of €35,000/QALY (4, 9). This vaccination strategy is already implemented in Belgium.
Additionally, as mentioned before, the WHO has a global strategy to eliminate CC by 2040. It is aimed at a world where CC is eliminated as a public health problem by reaching and maintaining an incidence rate of 4 per 100,000 women (26). As described before, HPV vaccination in Belgium exhibits significant regional disparities. Consequently, considering the WHO target of 90% of girls being fully vaccinated with an HPV vaccine by the age of 15, vaccination coverage in the Wallonia-Brussels region is suboptimal (55.1% for girls and 49.5%) (26). This advocates for strategies to increase the vaccination rate, especially in regions with lower coverage. Tailoring interventions to address specific regional challenges and cultural factors will be crucial in achieving equitable HPV vaccination coverage across Belgium.
In conclusion, GNV is economically attractive, particularly when accounting for additional HPV-related diseases, lower girl-only uptake rates, and cost-reducing measures. Specifically, GNV with the 9vHPV vaccine significantly reduces HPV-related disease incidence, deaths, and healthcare costs compared to FOV with either the 9vHPV or 2vHPV vaccines. Belgium is actively implementing measures in line with the WHO's global strategy to eliminate CC. Ongoing efforts in vaccination, screening, and public awareness are crucial to achieving the set targets and reducing the burden of CC in the country.
Envisioning a future where HPV-related cancers are eliminated, the necessity for routine CC screening would diminish significantly. This reduction could lead to the extension of screening intervals, resulting in substantial cost savings for healthcare systems. Additionally, continued vaccination efforts would be essential to prevent the reemergence of the virus. Sustaining high vaccination coverage would help maintain herd immunity, thereby protecting individuals who are unvaccinated or those in whom the vaccine is less effective. While initial investments in widespread vaccination and screening programs are substantial, the long-term savings from decreased cancer incidence and the potential for less frequent screening could offset these costs. Importantly, it is imperative to continue robust vaccination and screening programs to control and ultimately eliminate HPV-related diseases
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BE-NON-02524. Date of last revision: 04/2025.