Low methylation levels among HPV-vaccinated women with cervical HSIL 155 7 and considered significant at the p value < 0.05 level. Analyses were done with STATA/SE version 16.1 (Stata Corp., College Station, TX, USA). RESULTS The study population consisted of 403 HPV-vaccinated women born between 1992 and 1995, who participated in Finnish community and individually randomised trial cohorts, representing a population-based, country-wide HPV vaccination and cervical cancer screening trial established in 2007 20, 22. Among them, 15 had histology confirmed LSIL and 17 had HSIL. The mean time from cervical sample collection to colposcopy for LSIL cases was 12.9 months (range 0.8 to 44.3 months) and for HSIL cases was 8.3 months (range 1.0 to 41.3 months). Among the vaccinated HSIL cases, nine had HSIL Pap cytology recorded, with two cases of atypical glandular cells, not otherwise specified (AGC-NOS), and three atypical squamous cells, cannot rule out HSIL (ASC-H) pap cytology. All vaccinated LSIL/HSIL cases had negative for intraepithelial lesion or malignancy (NILM) or atypical squamous cells of undetermined significance (ASC-US) pap cytology recorded at the earlier follow-up visit at the age of 22. The vaccination age varied slightly between vaccinated HSIL cases and controls, with a mean age of 15.0 years compared to 14.6 years (Table 7.1). In the vaccinated HSIL cases, the majority of women were from the 1992 or 1994 birth cohorts (both 41.2%). Regarding HPV status, all vaccinated LSIL/HSIL cases had a higher overall HPV prevalence (86.7% and 88.2%, respectively) compared to controls (38.0%). Significant observations were seen among any hrHPV genotypes (88.2% and 80.0%) compared to controls (26.4%). The most common HPV genotype among vaccinated HSIL cases was HPV52 (n = 5, 29.4%), followed by HPV59, HPV51 and HPV58 (all n = 4, 23.5%), and HPV33 (n = 3, 17.7%). No HPV16/18 genotypes were observed. Multiple HPV infections were significantly more prominent among all HPV-vaccinated HSIL/LSIL cases (52.6-53.3%) compared to controls (16.2%). Eight (47.1%) women had a persistent type-specific HPV infection (HPV33, 35, 51, 52 or 59) recorded prior to colposcopy referral at the age of 18 and/or 22 years (Table 7.2). DNA methylation was evaluated among all 403 women for viral (HPV16, 18, 31 and 33) and host-cell genes (EPB41L3, FAM19A4 and miR124-2) (Figure 7.1). None of these separate DNA methylation markers showed significant differences between vaccinated controls
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