Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide.
Human papillomavirus 18 (HPV18) is the second most carcinogenic HPV type, after HPV16, and it accounts for approximately 12% of squamous cell carcinoma (SCC) as well as 37% of adenocarcinoma (ADC) of the cervix worldwide. We aimed to evaluate the worldwide diversity and carcinogenicity of HPV18 genetic variants by sequencing the entire long control region (LCR) and the E6 open reading frame of 711 HPV18-positive cervical samples from 39 countries, taking advantage of the International Agency for Research on Cancer biobank. A total of 209 unique HPV18 sequence variants were identified that formed three phylogenetic lineages (A, B, and C). A and B lineages each divided into four sublineages, including a newly identified candidate B4 sublineage. The distribution of lineages varied by geographical region, with B and C lineages found principally in Africa. HPV18 (sub)lineages were compared between 453 cancer cases and 236 controls, as well as between 81 ADC and 160 matched SCC cases. In region-stratified analyses, there were no significant differences in the distribution of HPV18 variant lineages between cervical cancer cases and controls or between ADC and SCC. In conclusion, our findings do not support the role of HPV18 (sub)lineages for discriminating cancer risk or explaining why HPV18 is more strongly linked with ADC than SCC.


OBJECTIVE
This is the largest and most geographically/ethnically diverse study of the genetic variation of HPV18 to date, providing a comprehensive reference for phylogenetic classification of HPV18 sublineages for epidemiological and biological studies.
International Agency for Research on Cancer, Lyon, France.
Alyce A
AA
Chen
International Agency for Research on Cancer, Lyon, France.
Tarik
T
Gheit
International Agency for Research on Cancer, Lyon, France.
Silvia
S
Franceschi
International Agency for Research on Cancer, Lyon, France tommasinom@iarc.fr cliffordg@iarc.fr.
Massimo
M
Tommasino
International Agency for Research on Cancer, Lyon, France tommasinom@iarc.fr cliffordg@iarc.fr.
Gary M
GM
Clifford
D000230:Adenocarcinoma / Q000453:epidemiology* / Q000208:ethnology / Q000473:pathology / Q000821:virology; D018070:Biological Specimen Banks; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000208:ethnology / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D052161:Human papillomavirus 18 / Q000145:classification / Q000235:genetics*; D006801:Humans; D058889:Molecular Typing; D009856:Oncogene Proteins, Viral / Q000235:genetics; D016366:Open Reading Frames; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000208:ethnology / Q000473:pathology / Q000821:virology; D010802:Phylogeny; D058974:Phylogeography; D044469:Racial Groups; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000473:pathology / Q000821:virology
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral