Human papillomavirus (HPV) genotype 53 is classified taxonomically in alpha HPV genus–species 6, together with HPV‐30, HPV‐56, and HPV‐66 and is considered to be one of three “probable high‐risk” HPV genotypes. Recent worldwide comparison of 44 isolates of HPV‐53 showed the existence of nine long control region (LCR) genomic variants, which formed a phylogenetic tree with two deep dichotomic branches. In order to investigate further the genomic diversity of HPV‐53, a total of 94 isolates of HPV‐53 obtained from an ethnogeographically closed cohort of 70 white European women was analyzed. The identification and characterization of HPV‐53 genomic variants was based on analysis of three different HPV genomic regions: LCR, E6 and E7. A higher genomic diversity of HPV‐53 was identified in the ethnogeographically closed cohort of white European women than has been reported previously on isolates collected worldwide. Altogether, 19 HPV‐53 genomic variants, composed of 13 LCR, 13 E6, and 5 E7 genomic variants, were identified. Eleven out of 13 LCR, all E6, and four out of five E7 genomic variants were described for the first time. The present study confirmed dichotomic phylogeny of HPV‐53 described previously and, in addition, showed for the first time that after a dichotomic split, both groups of HPV‐53 genomic variants formed star‐like phylogenetic clusters. In women with persistent HPV‐53 infection, HPV‐53 genomic variants remained unchanged for up to 51 months. In rare cases, infection with multiple HPV‐53 genomic variants is possible. Taking into account the results of this and previous studies, at least 26 different HPV‐53 genomic variants exist today. J. Med. Virol. 79:431–438, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]