|Grant Number:||5U01CA078527-15 Interpret this number|
|Primary Investigator:||Burk, Robert|
|Organization:||Albert Einstein College Of Medicine|
|Project Title:||Persistent HPV in Women at Risk for Cervix Cancer|
DESCRIPTION (provided by applicant): We are now in an era of an FDA approved prophylactic HPV16/18 vaccine for the two major types of HPV causing cervix cancer. Nevertheless, there are many critical questions about the natural history of non-HPV16/18 HPV types associated with cervix cancer and the fine specificity of the vaccine that remain and need to be addressed. The central hypothesis of this application is that DNA mutation and natural selection have driven the evolution of success amongst HPV infections resulting also in the emergence of cancer causing viruses, as a byproduct of filling a specific biological niche. We will utilize epidemiological methods and the analytic tools of evolution and systems biology to study the role of oncogenic HPV types and variants in population-based studies of HPV natural history and cervix neoplasia. We propose 3 specific aims: (1) To define the natural history of the a7 (18-related) and a9 (16-related) HPV types in the HPV Persistence and Progression (PaP) Cohort at Kaiser Permanente Northern California, a new cohort study of 35,000 HR-HPV positive (HC2+) women z 30 yrs of age women and in the 21,000 women from the Portland study with 16 years of follow-up; (2) To determine vaccine efficacy for HPV16/18-variants and related type variants after vaccination with HPV16/18 VLPs in the Costa Rica Vaccine Trial (CVT), a phase III HPV 16/18 vaccine trial of 7500 women 18-25 years of age in Guanacaste; and (3) To identify the genetic basis for the oncogenicity of high-risk HPV types and variants. There is a gradient of oncogenic risk from the most oncogenic, HPV16, to less oncogenic types (e.g., HPV31/35/45/56) to non-oncogenic (e.g., HPV53/70) HPV types within the "oncogenic" species groups a.5-7, a9 and a11. We will infer full viral genome sequence from variant "haplotype" information. This data will be combined with pathologic state and/or case-control status from the results generated in the cohort studies to determine genotype-phenotype relationships using a variety of phylogenetic and analytic approaches. Overall the data will provide important information on phenotypic-genetic relationships.
HPV16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer.
Authors: Mirabello L, Frimer M, Harari A, McAndrew T, Smith B, Chen Z, Wentzensen N, Wacholder S, Castle PE, Raine-Bennett T, Schiffman M, Burk RD
Source: Int J Cancer, 2015 Feb 15;136(4), p. E146-53.
EPub date: 2014 Sep 3.
Human papillomavirus 16 non-European variants are preferentially associated with high-grade cervical lesions.
Authors: Freitas LB, Chen Z, Muqui EF, Boldrini NA, Miranda AE, Spano LC, Burk RD
Source: PLoS One, 2014;9(7), p. e100746.
EPub date: 2014 Jul 1.
Lactobacillus crispatus dominant vaginal microbiome is associated with inhibitory activity of female genital tract secretions against Escherichia coli.
Authors: Ghartey JP, Smith BC, Chen Z, Buckley N, Lo Y, Ratner AJ, Herold BC, Burk RD
Source: PLoS One, 2014;9(5), p. e96659.
EPub date: 2014 May 7.
Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences.
Authors: Jelen MM, Chen Z, Kocjan BJ, Burt FJ, Chan PK, Chouhy D, Combrinck CE, Coutlée F, Estrade C, Ferenczy A, Fiander A, Franco EL, Garland SM, Giri AA, González JV, Gröning A, Heidrich K, Hibbitts S, Ho?njak L, Luk TN, Marinic K, Matsukura T, Neumann A, O?trbenk A, Picconi MA, Richardson H, Sagadin M, Sahli R, Seedat RY, Seme K, Severini A, Sinchi JL, Smahelova J, Tabrizi SN, Tachezy R, Tohme S, Uloza V, Vitkauskiene A, Wong YW, Zidovec Lepej S, Burk RD, Poljak M
Source: J Virol, 2014 Jul;88(13), p. 7307-16.
EPub date: 2014 Apr 16.
Human papillomavirus 33 worldwide genetic variation and associated risk of cervical cancer.
Authors: Chen AA, Heideman DA, Boon D, Chen Z, Burk RD, De Vuyst H, Gheit T, Snijders PJ, Tommasino M, Franceschi S, Clifford GM
Source: Virology, 2014 Jan 5;448, p. 356-62.
EPub date: 2013 Nov 12.
Human papillomavirus genome variants.
Authors: Burk RD, Harari A, Chen Z
Source: Virology, 2013 Oct;445(1-2), p. 232-43.
EPub date: 2013 Aug 31.
Evolution and taxonomic classification of alphapapillomavirus 7 complete genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70.
Authors: Chen Z, Schiffman M, Herrero R, DeSalle R, Anastos K, Segondy M, Sahasrabuddhe VV, Gravitt PE, Hsing AW, Burk RD
Source: PLoS One, 2013;8(8), p. e72565.
EPub date: 2013 Aug 16.
Oral human papillomavirus detection in older adults who have human immunodeficiency virus infection.
Authors: Fatahzadeh M, Schlecht NF, Chen Z, Bottalico D, McKinney S, Ostoloza J, Dunne A, Burk RD
Source: Oral Surg Oral Med Oral Pathol Oral Radiol, 2013 Apr;115(4), p. 505-14.
EPub date: 2013 Jan 31.
Association between hTERT activation by HPV E6 proteins and oncogenic risk.
Authors: Van Doorslaer K, Burk RD
Source: Virology, 2012 Nov 10;433(1), p. 216-9.
EPub date: 2012 Aug 25.
The cervical microbiome over 7 years and a comparison of methodologies for its characterization.
Authors: Smith BC, McAndrew T, Chen Z, Harari A, Barris DM, Viswanathan S, Rodriguez AC, Castle P, Herrero R, Schiffman M, Burk RD
Source: PLoS One, 2012;7(7), p. e40425.
EPub date: 2012 Jul 9.
Characterization of human papillomavirus type 120: a novel betapapillomavirus with tropism for multiple anatomical niches.
Authors: Bottalico D, Chen Z, Kocjan BJ, Seme K, Poljak M, Burk RD
Source: J Gen Virol, 2012 Aug;93(Pt 8), p. 1774-9.
EPub date: 2012 May 2.
Effectiveness of a simple rapid human papillomavirus DNA test in rural Nigeria.
Authors: Gage JC, Ajenifuja KO, Wentzensen N, Adepiti AC, Stoler M, Eder PS, Bell L, Shrestha N, Eklund C, Reilly M, Hutchinson M, Wacholder S, Castle PE, Burk RD, Schiffman M
Source: Int J Cancer, 2012 Dec 15;131(12), p. 2903-9.
EPub date: 2012 Apr 27.