Fig 1.
The steps within the green middle box are part of the cervical cancer screening program in Örebro County, Sweden, where women 30 years and older are screened with primary HPV. All mRNA-positive results lead to reflex cytology analysis on the same sample with liquid-based cytology (LBC) method. For this study, all HPV mRNA–positive samples were subjected to full DNA genotyping (left) and methylation analysis of the host genes FAM19A4 and miR-124-2 (right).
Fig 2.
Presentation of results from DNA genotyping from detected high-risk and low-risk HPV in both single- and multiple-genotype–positive samples in the screening population of women 30 years and older in Örebro, Sweden. A. All samples combined with numbers presented in the bar chart and proportions in table above. B. Samples among controls (normal cytology, ≤LSIL cytology, LSIL histology, and normal histology), including genotypes included in Aptima. C. Samples among cases (≥HSIL histology), including genotypes included in Aptima. HPV genotype is presented on the x-axis and number of positives for respective genotype on the y-axis. Blue bars constitute genotypes detected in samples with only one genotype (GT), and red bars represent GTs detected in samples containing more than one GT (multiple GT).
Table 1.
HPV genotype distribution in groups of screening outcome.
The HPV groups presented were positive vs. negative genotyping test, single vs. multiple genotypes within positive samples, positive for IARC1 genotype vs. positive for other non-IARC1 genotype, single vs. multiple IARC1 genotype within IARC1 positive samples, and HPV16/18 positive vs. positive for other IARC1 genotype. Results from statistical comparisons (Pearson Chi2) of proportions between the groups are presented in addition to strata analyses by age group in comparison of proportions between age groups (Fisher’s exact test). Total numbers of samples per category are presented in brackets by each category.
Table 2.
A. Results from FAM19A4/miR-124-2 hypermethylation analysis.
Presented in comparison between groups of differing age, screening outcome, and HPV status. The HPV groups presented were positive vs. negative genotyping test, single vs. multiple genotypes within positive samples, positive for IARC1 genotype vs. positive for other non-IARC1 genotype, single vs. multiple IARC1 genotype within IARC1 positive samples, and HPV16/18 positive vs. positive for other IARC1 genotype. B. Multivariate analysis. Binary logistic regression analysis of predictive factors for hypermethylation positivity in the FAM19A4 and hsa-miR124-2 genes.
Fig 3.
Genotype-specific hypermethylation patterns in samples among controls (normal cytology, ≤LSIL cytology, LSIL histology, and normal histology) and cases (≥HSIL histology).