Assessing the risk of cervical neoplasia in the post-HPV vaccination era

Abstract

This review is based on the recent EUROGIN scientific session: "Assessing risk of cervical cancer in the post-vaccination era," which addressed the demands of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesion (SIL) triage now that the prevalence of vaccine-targeted oncogenic high-risk (hr) human papillomaviruses (HPVs) is decreasing. Change in the prevalence distribution of oncogenic HPV types that follows national HPV vaccination programs is setting the stage for loss of positive predictive value of conventional but possibly also new triage modalities. Understanding the contribution of the latter, most notably hypermethylation of cellular and viral genes in a new setting where most oncogenic HPV types are no longer present, requires studies on their performance in vaccinated women with CIN/SIL that are associated with nonvaccine HPV types. Lessons learned from this research may highlight the potential of cervical cells for risk prediction of all women's cancers.

Keywords: cervical cancer; epigenetics; gynecological cancers; human papillomavirus; methylation.

FIGURE 1

Community‐level human papillomavirus (HPV) prevalence distribution visualized using ecological β‐diversity analysis among young 18‐year‐old women 4 years after community‐randomized gender‐neutral (A) or girls‐only (B) HPV vaccination, and control communities where hepatitis B‐virus vaccination was implemented (C). Arm A/B communities cluster separately from the control arm C communities mostly due to depletion of vaccine‐targeted HPV types 16/18/31/45 in the intervention A and B communities but also due to differential clustering driven by the not vaccine‐targeted HPV types 51/58/59. White dots represent HPV types community‐level prevalence distribution in two dimensions of the dissimilarity matrix with the blue (A), yellow (C) and gray (C) dots representing each of the 11 communities in each trial arm. The elliptic circles represent the overall diversity among the gender‐neutral (A) or girls‐only (B) HPV vaccinated and control (C) communities, respectively. Original HPVs prevalence data has been previously described by Gray et al and Louvanto et al

FIGURE 2

Finnish community and individually‐randomized trial cohorts with population‐based, country‐wide human papillomavirus (HPV) vaccination and cervical screening of 1992 to 1995 birth cohorts since 2007

FIGURE 3

Utilizing DNA methylation signatures in easy to access epithelial cell containing cervical smear samples to predict the risk of (screen) all four women cancers