Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women

BMC Infectious Diseases

Anna-Lise Williamson⁵  Ulf Gyllensten¹  David Coetzee³  Jennifer R Moodley⁴  Inger Gustavsson¹  Dianne J Marais²  Leigh F Johnson³  Zizipho ZA Mbulawa⁶ 

[1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, S-751 85 Uppsala, Sweden;Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa;Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa;School of Public Health and Family Medicine, Women’s Health Research Unit, University of Cape Town, Cape Town, South Africa;National Health Laboratory Service, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa;Center for HIV and STIs, National Institute for Communicable Disease, National Health Laboratory Service, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa

关键词: Viral load;    Human immunodeficiency virus;    Human papillomavirus;   

Others  :  1134816
DOI  :  10.1186/1471-2334-14-51

 received in 2013-01-17, accepted in 2014-01-22,  发布年份 2014

【 摘 要 】

Background

Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities.

Methods

Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-time polymerase chain reaction.

Results

HIV-positive women had a significantly higher viral load for combined alpha-9 HPV species compared to HIV-negative women (median 3.9 copies per cell compared to 0.63 copies per cell, P = 0.022). This was not observed for individual HPV types. HIV-positive women with CD4 counts >350/μl had significantly lower viral loads for alpha-7 HPV species (median 0.12 copies per cell) than HIV-positive women with CD4 ≤350/μl (median 1.52 copies per cell, P = 0.008), but low CD4 count was not significantly associated with increased viral load for other HPV species. High viral loads for alpha-6, alpha-7 and alpha-9 HPV species were significant predictors of abnormal cytology in women.

Conclusion

HIV co-infection significantly increased the combined alpha-9 HPV viral load in women but not viral loads for individual HPV types. High HR-HPV viral load was associated with cervical abnormal cytology.

【 授权许可】

   
2014 Mbulawa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Castellsague X, Diaz M, de Sanjose S, Munoz N, Herrero R, Franceschi S, et al.: Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 2006, 98:303-315.
• [2]Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, et al.: Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst 1999, 91:226-236.
• [3]Munoz N, Castellsague X, de Gonzalez AB, Gissmann L: HPV in the etiology of human cancer. Vaccine 2006, 24:1-10.
• [4]Palefsky J: HPV infection and HPV-associated neoplasia in immunocompromised women. Int J Gynecol Obstet 2006, 94:S56-S64.
• [5]Lomalisa P, Smith T, Guidozzi F: Human immunodeficiency virus infection and invasive cervical cancer in South Africa. Gynecol Oncol 2000, 77:460-463.
• [6]Levi JE, Kleter B, Quint WGV, Fink MCS, Canto CLM, Matsubara R, et al.: High prevalence of human papillomavirus (HPV) infections and high frequency of multiple HPV genotypes in human immunodeficiency virus-infected women in Brazil. J Clin Microbiol 2002, 40:3341-3345.
• [7]Fontaine J, Hankins C, Money D, Rachlis A, Pourreaux K, Ferenczy A, et al.: Human papillomavirus type 16 (HPV-16) viral load and persistence of HPV-16 infection in women infected or at risk for HIV. J Clin Virol 2008, 43:307-312.
• [8]Delmas MC, Larsen C, van Benthem B, Hamers FF, Bergeron C, Poveda JD, et al.: Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. Aids 2000, 14:1775-1784.
• [9]Harris TG, Burk RD, Palefsky JM, Massad LS, Bang JY, Anastos K, et al.: Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results. JAMA-J Am Med Assoc 2005, 293:1471-1476.
• [10]Ho CM, Cheng WF, Chu TY, Chen CA, Chuang MH, Chang SF, et al.: Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix. Br J Cancer 2006, 95:1384-1389.
• [11]Peitsaro P, Johansson B, Syrjanen S: Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique. J Clin Microbiol 2002, 40:886-891.
• [12]Schulz KF, Grimes DA: Sample size calculations in randomised trials: mandatory and mystical. Lancet 2005, 365:1348-1353.
• [13]Mbulawa ZZA, Coetzee D, Marais DJ, Kamupira M, Zwane E, Allan B, et al.: Genital human Papillomavirus prevalence and human Papillomavirus concordance in heterosexual couples are positively associated with human immunodeficiency virus coinfection. J Infect Dis 2009, 199:1514-1524.
• [14]Gustavsson I, Juko-Pecirep I, Backlund I, Wilander E, Gyllensten U: Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low grade dysplasia. J Clin Virol 2009, 45:85-89.
• [15]Levi G, Feldman J, Holman S, Salarieh A, Strickler HD, Alter S, et al.: Relationship between HIV viral load and Langerhans cells of the cervical epithelium. J Obstet Gynaecol Res 2005, 31:178-184.
• [16]Swan DC, Tucker RA, Tortolero-Luna G, Mitchell MF, Wideroff L, Unger ER, et al.: Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Microbiol 1999, 37:1030-1034.
• [17]Luchters SM, Vanden Brorck D, Chersich MF, Nel A, Delva W, Mandaliya K, et al.: Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers. BMC Infec Dis Ref Type: Generic 2010, 10:18. BioMed Central Full Text
• [18]Theiler RN, Farr SL, Karon JM, Paramsothy P, Viscidi R, Duerr A, et al.: High-risk human papillomavirus reactivation in human immunodeficiency virus-infected women risk factors for cervical viral shedding. Obstet Gynecol 2010, 115:1150-1158.
• [19]Strickler HD, Burk RD, Fazzari M, Anastos K, Minkoff H, Massad LS, et al.: Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst 2005, 97:577-586.
• [20]Viscidi RP, Snyder B, Cu-Uvin S, Hogan JW, Clayman B, Klein RS, et al.: Human papillomavirus capsid antibody response to natural infection and risk of subsequent HPV infection in HIV-positive and HIV-negative women. Cancer Epidemiol Biomarkers Prev 2005, 14:283-288.
• [21]Denny L, Boa R, Willimson AL, Allan B, Hardie D, Stan R, et al.: Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women. Obstet Gynecol 2008, 111:1380-1387.
• [22]Moberg M, Gustavsson I, Wilander E, Gyllensten U: High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer 2005, 92:891-894.
• [23]Sun XW, Kuhn L, Ellerbrock TV, Chiasson MA, Bush TJ, Wright TC: Human papillomavirus infection in women infected with the human immunodeficiency virus. New Engl J Med 1997, 337:1343-1349.
• [24]Gravitt PE, Kovacic MB, Herrero R, Schiffman M, Bratti C, Hildesheim A, et al.: High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. Int J Cancer 2007, 121:2787-2793.
• [25]Ho GYF, Studentsov YY, Bierman R, Burk RD: Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev 2004, 13:110-116.
• [26]Andersson S, Safari H, Mints M, Lewensohn-Fuchs I, Gyllensten U, Johansson B: Type distribution, viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer (CIN). Br J Cancer 2005, 92:2195-2200.