Singapore implemented a successful school-based human papillomavirus (HPV) vaccination program in 2019, achieving over 90% coverage among adolescent girls. However, this initiative leaves a substantial cohort of older women without systematic protection against HPV-related diseases. The specific problem addressed by this study is the long-term cancer burden among women who were too old to benefit from the school program. We aimed to evaluate the potential impact of extending high vaccination coverage to these older cohorts.
This issue is directly relevant to population oral health because HPV infection is increasingly recognized as a primary driver of oropharyngeal cancers. While cervical cancer prevention remains the traditional focus of HPV vaccination, the rising incidence of throat cancers represents a significant and underappreciated challenge within dental health and broader healthcare systems. Reducing the prevalence of HPV through targeted catch-up programs offers a mechanism to mitigate the future incidence of oropharyngeal malignancies. A quantitative projection of these long-term outcomes is necessary. It provides the evidence base required to justify the expansion of current vaccination policies to protect populations at risk.
What Was Done
We conducted a mathematical simulation study using a Proportional Multistate Life Table (PMSLT) model to project the long-term cancer burden under different vaccination scenarios. The model tracked a cohort of Singaporean females from age 12 to 100, simulating their annual transitions between four defined health states: healthy, developing cancer (cervical or oropharyngeal), remission, and death from cancer or other causes.
flowchart LR
H(["🟢 Healthy"]) -->|Develops cancer| C(["🔴 Cancer<br>Cervical or Oropharyngeal"])
H -->|Background mortality| D(["💀 Death<br>Other Causes"])
C -->|Remission| H
C -->|Cancer mortality| DC(["💀 Death<br>From Cancer"])
C -->|Background mortality| D
style H fill:#d4edda,stroke:#28a745,color:#000
style C fill:#f8d7da,stroke:#dc3545,color:#000
style D fill:#e2e3e5,stroke:#6c757d,color:#000
style DC fill:#e2e3e5,stroke:#6c757d,color:#000
Figure 1: The model’s health states. Each person in the simulated cohort can occupy one of four states at any given age and can transition between them annually.
The analytical approach compared three distinct scenarios starting from a 2022 baseline. The “Business as Usual” scenario assumed vaccination coverage remained at current levels with a slow natural decline in HPV. The “Gradual Catch-Up” scenario modelled an increase to 90% coverage over 15 years, targeting women aged 17 and older. The theoretical “HPV Eradication” scenario assumed HPV prevalence was reduced to zero over 15 years. This established a ceiling for potential health gains.
flowchart TD
Start(["📅 2022 Baseline<br>Vaccination coverage: ~15%<br>in women aged 18+"]) --> BAU
Start --> CU
Start --> ER
BAU(["📊 Business as Usual<br>Coverage stays flat<br>Natural slow decline in HPV"])
CU(["💉 Gradual Catch-Up<br>Coverage rises to 90%<br>over 15 years<br>Targets women 17+<br>not covered by school program"])
ER(["🎯 HPV Eradication<br>HPV prevalence reduced<br>to zero over 15 years<br>Theoretical best-case"])
BAU --> R1["Baseline cancer<br>trajectory"]
CU --> R2["~169,000 cancers<br>averted"]
ER --> R3["~191,000 cancers<br>averted (ceiling)"]
style BAU fill:#fff3cd,stroke:#ffc107,color:#000
style CU fill:#cce5ff,stroke:#0056b3,color:#000
style ER fill:#d4edda,stroke:#28a745,color:#000
Figure 2: The three scenarios compared in the model. The gradual catch-up and eradication scenarios both phase in over 15 years from 2022.
The primary analytical mechanism relied on the Population Impact Fraction. Reducing HPV prevalence proportionally decreased cancer incidence within the simulated cohort. A notable methodological strength of this study is the application of probabilistic sensitivity analysis. We ran the model 2,000 times, drawing key parameters such as incidence rates, relative risks, and case fatality rates from probability distributions. This approach rigorously quantified uncertainty and confirmed the stability of the projected outcomes.
Key Findings
A gradual catch-up vaccination program is projected to avert 164,968 cervical cancers (95% UI: 135,721 to 194,154) and 4,007 oropharyngeal cancers (95% UI: 3,036 to 4,966) over the cohort’s lifetime compared to business as usual.
The intervention would avert 4,083 cervical cancer deaths (95% UI: 2,922 to 5,190) and 396 oropharyngeal cancer deaths (95% UI: 248 to 548).
The catch-up strategy would generate 120,919 health-adjusted life years (95% UI: 89,459 to 150,325).
This realistic policy option captures approximately 89% of the theoretical maximum health benefit associated with complete HPV eradication.
The peak epidemiological impact occurs between ages 70 and 85, reflecting the long latency period between HPV infection and cancer manifestation.
What This Means for Policy
Singapore possesses the necessary infrastructure and public trust to maintain high HPV vaccination coverage in schools. The findings from this simulation indicate that extending this coverage to older cohorts is an effective public health strategy. The subsidized primary care network provides an established platform to reach women who were excluded from the initial school-based rollout.
Implementing a systematic catch-up program accelerates progress toward the World Health Organization target of elimination-level cervical cancer incidence, defined as fewer than four cases per 100,000 women annually. The data demonstrate that a realistic catch-up initiative captures nearly 90% of the theoretical maximum benefit. This represents a highly efficient policy choice compared to the current baseline trajectory.
There are substantial economic implications beyond the immediate health outcomes. Cervical and oropharyngeal cancers frequently affect individuals during their primary working years. Averting nearly 169,000 cancer cases translates to a massive reduction in direct healthcare expenditures, caregiver burden, and productivity losses. Policymakers must recognize that vaccination is a long-term investment. The upfront costs of expanding coverage will yield delayed but substantial dividends, primarily materializing when the treated cohort reaches late adulthood. The existing infrastructure and robust evidence base eliminate many of the typical barriers to implementation.
The evidence confirms that a targeted catch-up vaccination program is an efficient mechanism for reducing the future burden of HPV-related malignancies. What remains is the programmatic commitment to systematically reach the populations currently left unprotected to achieve long-term cancer elimination.
This research was funded by the Singapore Translational Research (STaR) Investigator Award (Marco A. Peres, 2023–2028) via the National Medical Research Council, and the Australian Research Council DECRA award (Ankur Singh, DE230101210).