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The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland

Abstract

Background

Understanding the pattern and dominance of HPV types in high grade cervical disease within increasingly vaccinated populations will help inform the development of appropriate screening and management protocols.

Methods

Over 1700 cases of cervical intraepithelial neoplasia (CIN) diagnosed between 2011 and 2017 in women younger than 25 were genotyped for HPV. Logistic regression was used to assess the association between HPV 16/18 positivity with biopsy-collection year, birth year, deprivation and vaccination status. Regression analysis was repeated for cross-protective types (31, 33 and 45). Type specific detail of non-vaccine types by vaccination status was presented descriptively.

Results

Detection of HPV 16/18 or 16/18/31/33 and 45 was lower in CIN2 associated with full vaccination vs no vaccination (OR 0.3; 95% CI 0.2–0.5 & 0.4; 95% CI 0.3–0.6 respectively) Similar observations were made for CIN3. The relative contribution of non-established high-risk types including those considered low risk was greater among vaccinated women with CIN2+ vs unvaccinated women with CIN2+.

Conclusions

The change in HPV distribution in CIN2+ in vaccinated populations is a further marker of vaccine impact. Additionally, the progression rate of CIN2+ in vaccinated populations may be lower given the shift in type distribution. The definition of high grade disease in vaccinated populations may warrant reassessment.

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Fig. 1: Cervical Intraepithelial Neoplasia cases included in final analysis after process of exclusion.
Fig. 2: Percentage appearance of HPV types detected in CIN2 and CIN3 according to vaccination status.
Fig. 3: Proportions of CIN2 and CIN3 cases associated with 4 categories of HPV.

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Data availability

Requests to access the aggregated data can be made to the corresponding author, any request for dissemination would need to follow due process of governance.

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Acknowledgements

The authors would like to thank the teams at the NHS Pathology Laboratories in Scotland that supported the field work and sample collation, the operational team at the Scottish HPV Reference Laboratory who supported with delivery of the HPV genotyping and Ms Helen Watson & Dr Kevin Pollock, previously based at Public Health Scotland for their contribution to early work on this initiative.

Funding

This work was funded by the Scottish Government.

Author information

Authors and Affiliations

Authors

Contributions

KC co-ordinated the fieldwork, sample collation and the laboratory testing and created the working manuscript draft, TP supported with data analysis and manuscript drafting, and provided critical comment on analysis, CG performed the statistical analysis and commented on early and later manuscript drafts, RC was involved in the initial planning of the work and provided input on study design, KR is lead for the HPV immunisation surveillance at Public Health Scotland, provided critical comment on analysis and contributed to manuscript drafting.

Corresponding author

Correspondence to Kate Cuschieri.

Ethics declarations

Competing interests

The work was performed as part of National HPV immunisation surveillance in Scotland, which is coordinated though Public Health Scotland (PHS). TP, RC and KR are employees of PHS. KC is Director of the Scottish HPV Reference Laboratory which is commissioned to deliver HPV testing and typing to inform Public Health surveillance. CG declares no competing interests.

Ethics approval and consent to participate

Records were anonymised before analysis, with preservation of linkage between immunisation and histology when appropriate. Caldicott Guardian approval, a UK process to ensure that the use of personal data complies with legal requirements for data protection and is in the public interest, was obtained for the use of data. The samples were generated through the routine activity of the Scottish cervical screening programme. Participation in the programme gives implied consent for the use of data derived from this participation for service monitoring and improvement. Management of individual patients was not affected by this study.

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The manuscript contains aggregate data only and does not contain person-level data.

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Cuschieri, K., Palmer, T., Graham, C. et al. The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland. Br J Cancer 129, 1134–1141 (2023). https://doi.org/10.1038/s41416-023-02386-9

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