Format

Send to

Choose Destination
Cell. 2017 Sep 7;170(6):1164-1174.e6. doi: 10.1016/j.cell.2017.08.001.

HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Electronic address: mirabellol@mail.nih.gov.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
4
Infections and Cancer Epidemiology Group, International Agency for Research on Cancer 150, Cours Albert Thomas, 69372 Lyon Cedex 08, France.
5
Sackler Institute for Comparative Genomics, American Museum of Natural History, New York City, NY, USA.
6
Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
7
Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong.
8
Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA, USA.
9
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
10
University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
11
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA; HealthCore Inc., Safety and Epidemiology, Wilmington, DE, USA.
12
Agencia Costarricense de Investigaciones Biomédicas (ACIB), former Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
13
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; Departments of Pediatrics, Microbiology and Immunology, and Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Abstract

Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

KEYWORDS:

E7 gene; HPV epidemiology; HPV genomics; HPV16; cervical carcinogenesis

PMID:
28886384
PMCID:
PMC5674785
DOI:
10.1016/j.cell.2017.08.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center