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Descriptive epidemiology of HPV in the post-vaccination era

Genotype distribution among positive samples in a post-vaccination setting, with an analysis by sample type to inform surveillance and screening

Sector

Public health and epidemiology

Client

Hospital microbiology department

Scope

Retrospective series 2020–2024

Deliverable

Epidemiological report with genotype analysis

Challenge

Characterising HPV genotype distribution in a post-vaccination setting and exploring signals of possible changes in circulation to inform screening

Generating local evidence on the current circulation of vaccine and non-vaccine genotypes to inform decisions on epidemiological surveillance and population screening.

Human papillomavirus (HPV), the main aetiological factor in cervical cancer, requires continuous epidemiological surveillance to assess the real impact of vaccination programmes. Since the introduction of routine vaccination covering high-risk genotypes, there had been uncertainty about the current distribution of vaccine versus non-vaccine genotypes in the health area, and about whether genotype replacement was taking place in a way that could compromise the effectiveness of screening.

The methodological challenge included analysing a large volume of positive samples collected over five years of opportunistic screening with molecular techniques, assessing differences in genotype distribution by sample type (endocervical versus vaginal swab), and quantifying the frequency and patterns of multiple coinfections. All of this to generate local descriptive evidence to guide further surveillance and screening assessments.

1,200+ samples

testing positive, with type-specific molecular genotyping

5 years

of continuous retrospective time series (2020–2024)

2 strategies

of sampling compared, with statistical significance by genotype

Solution

A retrospective descriptive epidemiological study on molecular genotyping data and a comparison of sampling strategies

Analysis of genotype distribution among positive samples

Single-centre retrospective observational study of more than 1,200 HPV-positive samples, genotyped by the microbiology department using nucleic acid amplification. Analysis of the stratified age distribution, differential genotype frequency among positive samples (vaccine vs non-vaccine), frequency of multiple coinfections and comparison by sample type.

Statistical methods with trend analysis

Descriptive analysis of demographic frequencies with measures of central tendency and dispersion. Fisher's exact tests to assess the association between sample type and the genotype detected. Pearson's correlation coefficient for genotype coinfection patterns. Analysis of time trends using monthly case series over five years, including a comparison of seasonality with other sexually transmitted infections.

Intervention frequency and genotype distribution by sample type

Analysis of the frequency of subsequent conisation by genotype detected, as an indicator of later clinical intervention. Comparison of differences in genotype distribution by sample type (endocervical versus vaginal swab). Assessment of vaginal self-sampling as a complementary strategy to extend population screening coverage.

Impact

Genotype patterns in a post-vaccination setting and evidence for screening

Predominance of non-vaccine genotypes among positive samples

Non-vaccine genotypes predominated among the positive samples. This pattern is compatible with changes in genotype circulation in the post-vaccination setting, but a descriptive design based on positive samples does not allow these changes to be attributed causally to vaccination, nor genotype replacement to be confirmed without a comparison with the pre-vaccination distribution in the same population. The genotype with the highest oncogenic risk (HPV-16) remains clinically relevant in both single infections and coinfections. The residual circulation of HPV-18 is consistent with international surveillance data.

Differences by sample type that inform screening

Genotype distribution differed by sample type, with a higher presence of vaccine genotypes in endocervical swabs and of non-vaccine genotypes in vaginal swabs. The association observed supports further evaluation of vaginal self-sampling as a complementary strategy, but does not on its own validate its diagnostic performance, which would require the total denominators for each method and an appropriate diagnostic reference standard.

Local evidence to inform vaccination and screening

The higher frequency of conisation associated with the genotype with the greatest oncogenic potential was consistent with the genotyping-based triage strategy, without on its own amounting to a validation of that strategy. Development of an analysis framework, reproducible in other health areas, to explore the effect of vaccination and guide the extension of genotyping in epidemiological surveillance programmes.

Project carried out under a confidentiality agreement. The client's identity has been withheld at their request.

Azahar's added value

What this case shows about the way we work

Molecular epidemiology of infectious diseases

Demonstrated capability in analysing genotype distribution from molecular genotyping data and in exploring possible changes in genotype circulation in populations with active vaccination programmes.

Evidence for evaluating screening strategies

Statistical analysis of differences in genotype distribution by sample type, providing evidence to guide public health decisions on complementary detection strategies.

Epidemiological surveillance to inform health policy

Generation of local quantitative evidence on genotype circulation that informs the evaluation of vaccine coverage and screening protocols in specific health areas.

Reproducible, scalable analysis frameworks

Design of a genotype surveillance methodology that can be replicated in other health areas, with a statistical pipeline that integrates genotype distribution analysis, time trends and comparison by sample type.

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