Human papillomavirus (HPV)16 is the most oncogenic HPV, responsible for most papillomavirus-induced anogenital cancers. HPV16 causes 70% of invasive cervical cancers (ICC) worldwide and a larger proportion of HPV related tumors of the anogenital region. HPV16 genetic diversity together with host genetics and target tissue largely determine the chances to trigger carcinogenesis.
We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers (cervix, vulva, vagina, ano, pene) from Europe, Asia, and Central/South America.
Tumor samples analysed in this study stem from a Formalin Fixed Paraffin Embedded repository from the Catalan Institute of Oncology (ICO), Barcelona, Spain . All samples were tested for the presence of tumour tissue, for the presence of HPV DNA using the SPF10-LiPA25 protocol (version 1; Laboratory Biomedical Products, Rijswijk, Netherlands) and (posar algo de com s'ha fet la determinació de les variants). We have assessed the contribution of geography, anatomy and histology (only ICC) to the differential prevalence of HPV16 variants Further, phylogenetic relationships of the E6, L2 and URR sequences generated from the samples in the global context of HPV16 genetic variability were inferred using an Evolutionary Placement Algorithm on RAxML_v7.2.8 with the GTR+Γ4 model .
The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3, except in Asia, where HPV16_A4 predominated in anal cancers.HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular invasive cervical cancer. We confirm further a non-random geographical structure of the viral variants distribution and histology in ICC.
Ther was a wide variation of HPV16 variants prevalence in anogenital cancers, partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers.
1: Nicolás-Párraga S, Alemany L, de Sanjosé S, Bosch FX, Bravo IG; RIS HPV TT and
HPV VVAP study groups. Differential HPV16 variant distribution in squamous cell
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May 1;140(9):2092-2100.
2: Nicolás-Párraga S, Gandini C, Pimenoff VN, Alemany L, de Sanjosé S, Xavier
Bosch F, Bravo IG; RIS HPV TT and HPV VVAP study groups. HPV16 variants
distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus.
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