Pan American Health Organization · 1st edition, 2023
Methodological guidance for measuring HPV vaccination programme impact on infection, precancerous lesions, and cervical cancer for programme managers and researchers.
- Issuer
- Pan American Health Organization
- Edition
- 1st edition, 2023
- Audience
- Immunization programme managers, public health officials, epidemiologists, researchers, pathologists, HPV laboratory personnel
- Evidence
- Expert consensus, methodological guidance synthesizing published impact studies and WHO/PAHO Technical Advisory Group recommendations
- Reviewed
- 17 Oct 2026 · GMJ
What this guideline says
GMJ summary
This PAHO technical manual provides conceptual and methodological guidance for evaluating the population-level impact of HPV vaccination programmes in Latin America and the Caribbean. As of December 2022, 47 countries and territories (92%) in the Americas have introduced HPV vaccines—the highest adoption rate globally—primarily targeting girls aged 9–14 years. The document prioritizes outcomes by relevance and feasibility: HPV infection prevalence (measurable 5+ years post-introduction), anogenital warts incidence (5–10 years, quadrivalent/nonavalent vaccines only), precancerous cervical lesions (10–15 years), and cervical cancer incidence and mortality (20+ years).
The manual emphasizes that accurate HPV vaccination coverage monitoring is a prerequisite for any impact assessment, and where coverage is suboptimal, increasing uptake takes priority over conducting impact studies. It details study designs (pre-/post-vaccine comparisons, time-trend analyses), sample-size calculations, required infrastructure (population-based cancer registries, HPV genotyping laboratories, screening programme data), and critical confounders including concurrent cervical screening programmes and changes in sexual behaviour. A decision algorithm guides selection of indicators based on available resources, years since programme launch, and existing data systems.
The document stresses that demonstrating vaccine impact with local evidence sustains political and financial commitment, enhances public and provider confidence, and supports programme improvement. Four biological outcomes are prioritized: vaccine type-specific HPV infection prevalence (requires HPV DNA/RNA detection and genotyping, sample size 200–18,000 depending on baseline prevalence and coverage), anogenital warts incidence (via STI surveillance or administrative databases), CIN2+ lesion incidence (requires pathology registries and stable screening protocols), and cervical cancer incidence/mortality (requires quality population-based cancer registries or vital statistics). The manual is intended for immunization programme managers, epidemiologists, public health officials, and researchers planning post-introduction evaluations.
Key points
For clinicians — doses and thresholds as stated in the guideline
- HPV vaccination coverage data by age must be accurate and available before undertaking any impact study; suboptimal coverage requires prioritizing uptake over evaluation.
- Vaccine type-specific HPV infection prevalence (HPV16/18) can be assessed 5–10 years post-introduction in women aged <25 years; sample size ranges from 200 (at 30% baseline prevalence, 90% coverage) to 18,000 (at 0.5% prevalence, 50% coverage) for 80% power.
- Anogenital warts incidence (for quadrivalent/nonavalent vaccines) is measurable 5–10 years post-introduction via sentinel STI clinics, primary-care databases, or hospital records; a control STI (e.g. chlamydia, first-episode herpes) should be monitored to detect changes in sexual behaviour independent of vaccination.
- Precancerous cervical lesions (CIN2+) incidence can be evaluated 10–15 years post-introduction, expressed as rate per women screened to adjust for screening participation; requires stable screening protocols and centralized histopathology registries.
- Cervical cancer incidence requires quality population-based cancer registries (IARC-accredited, included in Cancer Incidence in Five Continents); mortality requires vital statistics with <25% ill-defined cause-of-death codes and >80% coverage; both measurable 20+ years post-introduction.
- HPV detection/genotyping for impact studies requires validated assays allowing at least HPV16/18 individual genotyping, laboratory with quality control, trained personnel, and appropriate transport/storage of specimens (cervical, vaginal self-collection, or urine for feasibility).
- Impact studies compare disease frequency pre- and post-vaccine introduction in the same age groups and settings; confounders include changes in screening programme coverage/methods, sexual behaviour (number of partners, age at debut, condom use), and case detection/reporting systems.
- WHO 90–70–90 elimination targets by 2030: 90% of girls fully vaccinated by age 15; 70% of women screened with high-performance test by ages 35 and 45; 90% of women with cervical disease treated—impact measurement tracks progress toward these benchmarks.
Required sample size for estimating the impact of an HPV vaccination program on the prevalence of HPV16/18 infection in different scenarios of prevalence of HPV and coverage
Table extracted from the guideline
| Prevalence of HPV16/18 infection in the reference population | 90% coverage | 80% coverage | 70% coverage | 60% coverage | 50% coverage |
|---|---|---|---|---|---|
| 0.5% | 4 350 | 5 900 | 8 200 | 11 800 | 18 000 |
| 1% | 2 150 | 3 000 | 4 100 | 5 900 | 8 950 |
| 2% | 1 100 | 1 500 | 2 100 | 3 050 | 4 650 |
| 5% | 450 | 600 | 850 | 1 200 | 1 800 |
| 10% | 200 | 300 | 400 | 550 | 850 |
| 20% | 100 | 130 | 180 | 250 | 400 |
| 30% | 60 | 80 | 110 | 160 | 250 |
Source: Pan American Health Organization, Evaluating the impact of the human papillomavirus vaccine in Latin America and the Caribbean. Reproduced in summary form.
From the guideline
Verbatim
“Where HPV vaccination coverage is suboptimal, priority should be given to increasing HPV vaccination coverage in the target population before impact studies are conducted.”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As Editor-in-Chief of the Georgian Medical Journal and Chair of the Public Health Institute, I view this PAHO manual as directly applicable to Georgia's newly launched HPV vaccination programme (2024, quadrivalent vaccine for girls 9–14 years). Our immediate priority is establishing baseline HPV16/18 prevalence in young women—feasible through antenatal or reproductive health clinics in Tbilisi, Batumi, and regional centres—before the first vaccinated cohort reaches age 18 in 2033. I would stress to Georgian colleagues the recommendation to monitor coverage rigorously first: our National Immunization Programme must achieve and sustain ≥80% two-dose uptake before investing in impact studies, and nominal vaccination registries (already in place for routine childhood vaccines) should be adapted for HPV with linkage to the National Cancer Registry. One realistic caveat is laboratory capacity: HPV genotyping currently requires sending samples abroad; establishing in-country validated HPV DNA testing with at least HPV16/18 differentiation—essential for impact measurement—will require investment in molecular diagnostics, quality assurance, and trained personnel, potentially through regional collaboration with Armenia or partnerships with IARC reference laboratories. The manual's algorithm (Figure 5, page 40) prioritizing cervical cancer incidence only if a quality population-based cancer registry exists is a timely reminder that strengthening our cancer registry to meet IARC standards for Cancer Incidence in Five Continents inclusion is itself a prerequisite for long-term vaccine impact demonstration and supports broader cancer control policy.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 17 Oct 2026
Applicability
Georgia and the South Caucasus
Georgia introduced national HPV vaccination in 2024 (quadrivalent vaccine, girls aged 9–14), making this manual immediately relevant for planning future impact assessments. The South Caucasus and Eastern Europe face cervical cancer age-standardized incidence rates of 10–20 per 100,000 (higher than Western Europe’s 6–8), with mortality reflecting limited organized screening and late-stage diagnosis. For Georgia, establishing baseline HPV16/18 prevalence in women aged 18–24 before the first vaccinated cohort reaches that age (by 2033) is critical; opportunistic recruitment through antenatal or STI clinics is feasible given existing infrastructure. The manual’s emphasis on monitoring coverage first aligns with Georgia’s need to achieve >80% two-dose uptake in the initial years. Countries in the region with fragmented screening (opportunistic cytology, variable VIA/HPV test access) must account for screening programme heterogeneity as a confounder; linking vaccination registries to pathology and cancer registries (Georgia’s National Cancer Registry, established 2011, is not yet in Cancer Incidence in Five Continents Vol. XI) will be essential. The recommendation to use a control STI (chlamydia surveillance exists in Georgia via the National Center for Disease Control) to detect secular trends in sexual behaviour independent of vaccination is particularly relevant given sociocultural sensitivities around adolescent sexual health. For resource planning, the manual’s sample-size tables indicate that at 10% baseline HPV16/18 prevalence and 70% coverage, 400 women per time point would suffice—achievable through existing maternal-child health or reproductive health services. Regional collaboration (Armenia introduced HPV vaccine 2019, Azerbaijan not yet) could enable comparative impact studies and shared laboratory capacity for HPV genotyping, which currently requires international reference laboratory support in most settings.
Questions this guideline answers
Quick answers
When can we measure the impact of an HPV vaccination programme that started this year on cervical cancer incidence?
Cervical cancer incidence can be reliably assessed only 20 years or more after programme start, once vaccinated cohorts reach the peak age of cancer occurrence (≥30 years). Before then, assess short-term outcomes: HPV infection prevalence (5–10 years), anogenital warts (5–10 years, if using quadrivalent/nonavalent vaccine), or precancerous lesions (10–15 years). Any changes in cancer incidence observed before vaccinated cohorts reach age 30 reflect screening programme changes or other factors, not vaccination.
What sample size is needed to demonstrate a reduction in HPV16/18 infection prevalence after vaccine introduction?
It depends on baseline HPV16/18 prevalence and vaccine coverage. For example, at 5% baseline prevalence and 70% coverage, 850 women total (425 pre-vaccine, 425 post-vaccine) give 80% power at 5% significance assuming 90% vaccine efficacy. At lower baseline prevalence (1%) and 70% coverage, 4,100 are needed. The manual provides a full table (Table 8, page 33) for planning. Use pilot data or regional studies to estimate baseline prevalence before calculating final sample size.
Our country uses cytology-based screening, not HPV testing. Can we still measure vaccine impact on HPV infection?
Yes, but you must establish protocols for HPV sample collection, transport, and genotyping, as conventional cytology does not detect HPV types. Options include: recruiting women during routine screening and collecting an additional cervical or vaginal sample in liquid medium; using vaginal self-collection (acceptable, less sensitive with signal-amplification HPV assays but adequate with PCR-based tests); or partnering with chlamydia screening programmes that use suitable specimens. Ensure a validated HPV test with at least HPV16/18 individual genotyping, laboratory quality control, and trained personnel. Budget for these as new costs.
How do we account for the effect of cervical cancer screening when measuring HPV vaccine impact on precancerous lesions?
Express CIN2+ incidence as a rate per women screened (not per total population) to adjust for changes in screening participation. Include only women participating in screening programmes, document any changes in screening protocols (test type, age, intervals, treatment guidelines) over time, and adjust analyses for these changes or restrict comparisons to periods with stable protocols. The observed reduction in CIN2+ reflects the combined effect of vaccination and screening; you cannot fully separate them, but controlling for screening intensity and test sensitivity/specificity in the analysis minimizes confounding. If screening recommendations change substantially, consider measuring HPV infection or anogenital warts instead.
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- Issuer
- Pan American Health Organization
- Type
- Procedures, manuals, guidelines
- Edition
- 1st edition, 2023
- Status
- Current
- Published
- 2023-01-01
- Languages
- English
- Scope
- HPV vaccination programme impact evaluation (infection, anogenital warts, precancerous lesions, cervical cancer)
- Audience
- Immunization programme managers, public health officials, epidemiologists, researchers, pathologists, HPV laboratory personnel
- Licence
- CC BY-NC-SA 3.0 IGO
- ISBN
- 978-92-75-12739-1 (PDF)
- Evidence
- Expert consensus, methodological guidance synthesizing published impact studies and WHO/PAHO Technical Advisory Group recommendations
- Record history
- Created 17 Oct 2026 · updated 17 Oct 2026 · next check Apr 2027
Pan American Health Organization. Evaluating the impact of the human papillomavirus vaccine in Latin America and the Caribbean. Washington, D.C.: PAHO; 2023.GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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