Simplified representation of DNA methylation patterns during progression to cervical cancer. a Levels of DNA methylation across the genome of HPV16, adapted from figure 1A of Mirabello et al. [9]. The lines represent the median percentage of methylation averaged across discrete sets of CpG sites in each HPV16 genomic region. HPV16 contains 113 CpG sites (depending on the variant), and the levels depicted by the lines represent an approximate running average across the genome of HPV16, grouping adjacent (10-20) methylated CpGs. The levels of methylation of individual CpG sites are highly variable, with some CpG sites between other highly methylated sites showing no methylation. The bar at the bottom shows the various genomic regions, such as the upstream regulatory region (URR) and the early (E) and late (L) open reading frames of the HPV16 circular genome, which is shown here linearized in the URR for ease of visualization. b Median levels of DNA methylation of the human gene EPB41L3 and 2 CpG sites in HPV16 L1 (6,367 and 6,389; genomic positions as shown in a) as a function of histopathological diagnosis. The lower and upper edges of the boxes represent the 25th and 75th percentiles, respectively, while the horizontal white lines show the median methylation values, and the 5 and 95% values are shown by the lower and upper limits of the vertical lines, respectively. Adapted from figure 1 of Louvanto et al. [10]. CIN grades 1, 2 and 3 are represented by CIN1, CIN2 and CIN3, respectively. Cervical cancer is shown by SCC and cervical adenocarcinoma by ADC.