Keywords
HPV types
Cervical lesions
Molecular Epidemiology
Abstract
INTRODUCTION
Primary-prevention by prophylactic vaccination against HPV related cancers and HPV-based screening programs are based on HPV-type distribution in immunocompetent individuals. HIV-infected women are at high risk of invasive HPV-disease sustained by a broader range of HPV-types and have higher multi-type infection rates than immunocompetent hosts.
METHODS
This is a cross-sectional analysis of HR-HPV type distribution in 805 HIV+ women (HIW) compared with a control group of 1402 immunocompetent HIV- women (SPW) enrolled in the VALHIDATE study in order to define HPV type-specific distribution according to cytology.
RESULTS
HIW had a 3.8, 3.6, and 2.7 times higher risk of ASCUS, LSIL and HSIL than SPW respectively. HPV-DNA prevalence was 28.4% in HIW and 11.81% in SPW (p<0.0001). The prevalence of infection increased from normal cytology to HSIL both in HIW (from 21.45% to 90.91%) and SPW (from 9.54% to 75%). The OR for women with normal cytology of having a positive HPV DNA test result of was 2.6 times higher in HIW than in SPW. The cumulative prevalence of HPV-16/18 in HSIL is much lower in HIW (36.4±28.4) than SPW (62.5±33.5).
CONCLUSIONS
A higher prevalence of infection and broader HPV type distribution were observed in HIV+ women compared to the general population. More than 60% of HSIL lesions of HIW patients are caused by single or multi-type infections from non-HPV16/18 HPVs. The potential 9v-HPV vaccine coverage could be even higher than that expected for the general population given the wide panel of HPV-types observed in the HSIL of HIV+ women.
References
REFERENCES
International Agency for Research on Cancer (IARC). Human Papillomaviruses. IARC Monogr Eval Carcinog Risks Hum 2011;100B:261-319. Available online: http://monographs.iarc.fr/ENG/Monographs/vol100B/mono100B-1.pdf
Combes JD, Guan P, Franceschi S, Clifford GM. Judging the carcinogenicity of rare human papillomavirus types. Int J Cancer. 2015;136(3):740-2. doi: 10.1002/ijc.29019.
Wang SS, Zuna RE, Wentzensen N, Dunn ST, Sherman ME, Gold MA, Schiffman M, Wacholder S, Allen RA, Block I, Downing K, Jeronimo J, Carreon JD, Safaeian M, Brown D, Walker JL. Human papillomavirus cofactors by disease progression and human papillomavirus types in the study to understand cervical cancer early endpoints and determinants. Cancer Epidemiol Biomarkers Prev. 2009;18(1):113-20. doi: 10.1158/1055-9965.EPI-08-0591.
Rellihan MA, Dooley DP, Burke TW, Berkland ME, Longfield RN. Rapidly progressing cervical cancer in a patient with human immunodeficiency virus infection. Gynecol Oncol. 1990;36(3):435-8.
Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst. 2000;92(18):1500-10.
Levi JE, Kleter B, Quint WJV, Fink MCS, Canto CLM, Matsubara R, Linhares I, Segurado A, Vanderborght B, Neto JE, van Doorn LJ. High prevalance of human papilllomavirus (HPV) infections and high frequency of multiple HPV genotypes in human immunodeficiency virus-infected women in Brazil. J Clin Microbiol. 2002;40(9):3341-5. doi: 10.1128/JCM.40.9.3341-3345.2002.
Clifford GM, Gonclaves MA, Franchesci S, HPV and HIV Study Group. Human papillomavirus types among women infected with human immunodeficiency virus: a meta-analysis. AIDS. 2006;20(18):2337-44.
Garbuglia AR, Piselli P, Lapa D, Sias C, Del Nonno F, Baiocchini A, Cimaglia C, Agresta A, Capobianchi MR. Frequency and multiplicity of human papillomavirus infection in HIV-1 positive woman in Italy. J Clin Virol. 2012;54(2):141-6. doi: 10.1016/j.jcv.2012.02.013.
Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J,
Moreira ED, Ngan JY, Petersen LK, Lazcano‑Ponce E, Pitisuttithum P,
Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W,
Kjaer SK, Bautista OM, Chan ISF, Chen J, Gesser R, Moeller E, Ritter M,
Vuocolo S, Luxembourg A, for the Broad Spectrum HPV Vaccine Study. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–23. doi: 10.1056/NEJMoa1405044.
Serrano B, Alemany L, Tous S, Bruni L, Clifford GM, Weiss T, Bosch FX, de Sanjosé S. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer. 2012;7(1):38. doi: 10.1186/1750-9378-7-38.
Orlando G, Tanzi E, Chatenoud L, Gramegna M, Rizzardini G, VALHIDATE Study Group. Rationale and design of a multicenter prospective cohort study for the eVALuation and monitoring of HPV infections and relATEd cervical diseases in high-risk women (VALHIDATE study). BMC Cancer. 2012;12:204. doi: 10.1186/1471-2407-12-204.
Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T Jr, Young N, Forum Group Members, Bethesda 2001 Workshop. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114-9.
Tanzi E, Bianchi S, Fasolo MM, Frati ER, Mazza F, Martinelli M, Colzani D, Beretta R, Zappa A, Orlando G. High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping. J Med Virol. 2013;85: 91-8. doi: 10.1002/jmv.23434.
Bernard HU, Chan SY, Manos MM, Ong CK, Villa LL, Delius H, Peyton CL, Bauer HM, Wheeler CM. Identification and assessment of known and novel Human Papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis. 1994;170(5):1077-85.
Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J, Bosch FX, de Sanjosé S. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report 19 May 2017.
Keller MJ, Burk RD, Massad LS, Eltoum IE, Hessol NA, Castle PE, Anastos K, Xie X, Minkoff H, Xue X, D'Souza G, Flowers L, Levine AM, Colie C, Rahangdale L, Fischl MA, Palefsky JM, Strickler HD. Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test. Clin Infect Dis. 2015;61(10):1573-81. doi: 10.1093/cid/civ569.
McKenzie ND, Kobetz EN, Ganjei-Azar P, Rosa-Cunha I, Potter JE, Morishita A, Lucci JA, Guettouche T, Hnatyszyn JH, Koru-Sengul T. HPV in HIV-infected women: implications for primary prevention. Front Oncol. 2014;4:179. doi: 10.3389/fonc.2014.00179.
Castilho JL, Levi JE, Luz PM, Cambou MC, Vanni T, de Andrade A, Derrico M, Veloso VG, Grinsztejn B, Friedman RK. A cross-sectional study of high-risk human papillomavirus clustering and cervical outcomes in HIV-infected women in Rio de Janeiro, Brazil. BMC Cancer. 2015;15:478. doi: 10.1186/s12885-015-1486-4.
Tanzi E, Amendola A, Bianchi S, Fasolo MM, Beretta R, Pariani E, Zappa A, Frati E, Orlando G. Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy. Vaccine. 2009;27(S1):A17-23. doi: 10.1016/j.vaccine.2008.10.091
Sobota RS, Ramogola-Masire D, Williams SM, Zetola NM. Co-infection with HPV types from the same species provides natural cross-protection from progression to cervical cancer. Infect Agent Cancer. 2014;9:26. doi: 10.1186/1750-9378-9-26.
Serrano B, Alemany L, Ruiz PA, Tous S, Lima MA, Bruni L, Jain A, Clifford GM, Qiao YL, Weiss T, Bosch FX, de Sanjosé S. Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China). Cancer Epidemiol 2014;38(6):748-56. doi: 10.1016/j.canep.2014.09.003.