Predictable changes in the accuracy of human papillomavirus tests after vaccination: review with implications for performance monitoring in cervical screening

Br J Cancer. 2024 May;130(11):1733-1743. doi: 10.1038/s41416-024-02681-z. Epub 2024 Apr 13.

Abstract

Vaccination against human papillomavirus (HPV) is changing the performance of cytology as a cervical screening test, but its effect on HPV testing is unclear. We review the effect of HPV16/18 vaccination on the epidemiology and the detection of HPV infections and high-grade cervical lesions (CIN2+) to evaluate the likely direction of changes in HPV test accuracy. The reduction in HPV16/18 infections and cross-protection against certain non-16/18 high-risk genotypes, most notably 31, 33, and/or 45, will likely increase the test's specificity but decrease its positive predictive value (PPV) for CIN2+. Post-vaccination viral unmasking of non-16/18 genotypes due to fewer HPV16 co-infections might reduce the specificity and the PPV for CIN2+. Post-vaccination clinical unmasking exposing a higher frequency of CIN2+ related to non-16/18 high-risk genotypes is likely to increase the specificity and the PPV of HPV tests. The effect of HPV16/18 vaccination on HPV test sensitivity is difficult to predict based on these changes alone. Programmes relying on HPV detection for primary screening should monitor the frequency of false-positive and false-negative tests in vaccinated (younger) vs. unvaccinated (older) cohorts, to assess the outcomes and performance of their service.

Publication types

  • Review

MeSH terms

  • Early Detection of Cancer* / methods
  • Female
  • Human Papillomavirus Viruses
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology
  • Humans
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Infections* / virology
  • Papillomavirus Vaccines* / administration & dosage
  • Papillomavirus Vaccines* / immunology
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / prevention & control
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / prevention & control
  • Uterine Cervical Neoplasms* / virology
  • Vaccination

Substances

  • Papillomavirus Vaccines