Human Papillomavirus Vaccination and Screening in the Elimination of HPV-Associated Cancers: Evidence-Based Randomized Trials

Screening and Triage of Cervical Neoplasia in HPV-vaccinated Women

Author(s): Matti Lehtinen *

Pp: 48-59 (12)

DOI: 10.2174/9789815305487124010007

* (Excluding Mailing and Handling)

Abstract

 We have been running an individually randomized cervical screening trial since 2014. All 14,686 HPV-vaccinated women from birth cohorts 1992-1995, who had received three vaccine shots between 12 to 15 years of age (12,402) or at 18 years of age (2,284). They were invited to participate in an individually randomized trial on infrequent vs.frequent cervical screening visits at ages 22, 25 and 28. The infrequently screened arm participants are informed only on cytological findings indicative of colposcopy and conisation, i.e., high- grade squamous cervical intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). Furthermore, due to in-country migration female residents in one of the original 33 vaccination trial communities or after having moved to the Helsinki Metropolitan Region after 2014 were eligible. Altogether 6,958 women consented with a very high (over 92%) compliance to participate in the second (6,381 women) and the third (4,616 of 5,100 women vaccinated as early adolescents in 2007-2009) screening visits. The occurrence of cervical lesions: ASCUS, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ has been equal in the different arms. The progression potential of the HSIL findings in the HPV16/18 vaccinated women is probably reduced as suggested by the identification of hypermethylation of HPVindependent cervical cancer risk genes in only a few of the diagnosed HSIL cases. A randomized trial to compare mere clinical follow-up vs.treatment of HSILs diagnosed in vaccinated women is highly warranted.


Keywords: Cervical cancer, Epigenomics, Human papillomavirus, High-grade squamous intraepithelial lesion, Methylation, Screening.

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