Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

Cecily Banura, Florence M Mirembe, Anne R Katahoire, Proscovia B Namujju, Anthony K Mbonye, Fred M Wabwire, Cecily Banura, Florence M Mirembe, Anne R Katahoire, Proscovia B Namujju, Anthony K Mbonye, Fred M Wabwire

Abstract

Background: Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.

Methods: To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.

Results: Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections.Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.

Conclusion: Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.

References

    1. Ferlay J, Bray F, Parkin MD. IARC cancer Base. No. 5 version 2.0. IARC, Lyon; 2004. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide.
    1. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9. doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>;2-F.
    1. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. 1997;102(5A):3–8.
    1. Moscicki AB, Schiffman M, Kjaer S, Villa LL. Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine. 2006;24(Suppl 3):S3/42–51.
    1. Nielson CM, Flores R, Harris RB, Abrahamsen M, Papenfuss MR, Dunne EF, Markowitz LE, Giuliano AR. Human Papillomavirus Prevalence and Type Distribution in Male Anogenital Sites and Semen. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1107–14. doi: 10.1158/1055-9965.EPI-06-0997.
    1. IARC.
    1. Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJF, Meijer CJLM. the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Eng J Med. 2003;348:518–27. doi: 10.1056/NEJMoa021641.
    1. Lacey CJN, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24S3:S3/35–S3/41.
    1. The WHO/ICO Information Centre on HPV and Cervical Cancer.
    1. Parkin MD, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA: A Cancer J Clinicians. 2005;55(2):74–108. doi: 10.3322/canjclin.55.2.74.
    1. PATH. Cervical cancer vaccine. Cervical cancer.
    1. Mariani L. HPV-vaccine and screening programs: the new era of global prevention. J Preve Med Hyg. 2009;50:90–5.
    1. Cope U, Hildesheim A, Schiffman MH, Manos MM, Lorincz AT, Burk RD, Glass AG, Greer C, Buckland J, Helgesen K, Scott DR, Sherman ME, Kurman RJ, Liaw KL. Comparison of the hybrid capture tube test and PCR for detection of human papillomavirus DNA in cervical specimens. J Clin Microbiol. 1997;35(9):2262–5.
    1. Quint W, Pagliusi SR, Lelie N, de Villiers EM, Wheeler CM. the World Health Organization Human Papillomavirus DNA International Collaborative Study Group. Results of the First World Health Organization International Collaborative Study of Detection of Human Papillomavirus DNA. J Clin Microbiol. 2006;44(2):571–9. doi: 10.1128/JCM.44.2.571-579.2006.
    1. Chan PK, Cheung TH, Tam AO, Lo KW, Yim SF, Yu MM, To KF, Wong YF, Cheung JL, Chan DP, Hui M, Ip M. Biases in human papillomavirus genotype prevalence assessment associated with commonly used consensus primers. Int J Cancer. 2006;118(1):243–5. doi: 10.1002/ijc.21299.
    1. Banura C, Franceschi S, Doorn LJ, Arslan A, Wabwire-Mangen F, Mbidde EK, Quint W, Weiderpass E. Infection with human papillomavirus and HIV among young women in Kampala, Uganda. J Infect Dis. 2008;197(4):555–62. doi: 10.1086/526792.
    1. Blossom DB, Beigi RH, Farrell JJ, Mackay W, Qadadri B, Brown DR, Rwambuya S, Walker CJ, Kambugu FS, Abdul-Karim FW, Whalen CC, Salata RA. Human papillomavirus genotypes associated with cervical cytologic abnormalities and HIV infection in Ugandan women. J Med Virol. 2007;79(6):758–65. doi: 10.1002/jmv.20817.
    1. Banura C, Franceschi S, van Doorn LJ, Arslan A, Kleter B, Wabwire-Mangen F, Mbidde EK, Quint W, Weiderpass E. Prevalence, incidence and clearance of human papillomavirus infection among young primiparous pregnant women in Kampala, Uganda. Int J Cancer. 2008;123(9):2180–7. doi: 10.1002/ijc.23762.
    1. Taube JM, Kamira B, Motevalli M, Nakabiito C, Lukande R, Kelly DP, Erozan YS, Gravitt PE, Buresh ME, Mmiro F, Bagenda D, Guay LA, Jackson JB. Human papillomavirus prevalence and cytopathology correlation in young Ugandan women using a low-cost liquid-based Pap preparation. Diagn Cytopathol. 2010;38(8):555–63.
    1. Safaeian M, Kiddugavu M, Gravitt PE, Gange SJ, Ssekasanvu J, Murokora D, Sklar M, Serwadda D, Wawer MJ, Shah KV, Gray R. Prevalence and risk factors for carcinogenic human papillomavirus infections in rural Rakai, Uganda. Sex Transm Infect. 2008;84:306–311. doi: 10.1136/sti.2007.027318.
    1. Asiimwe S, Whalen CC, Tisch DJ, Tumwesigye E, Sethi AK. Prevalence and predictors of high-risk human papillomavirus infection in a population-based sample of women in rural Uganda. Int J STD AIDS. 2008;19(9):605–10. doi: 10.1258/ijsa.2008.008025.
    1. Clifford G, Smith JS, Aguado T, Franceschi S. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. British J Cancer. 2003;89:101–5. doi: 10.1038/sj.bjc.6601024.
    1. Smith JS, Melendy A, Rana RK, Pimenta JM. Age-specific prevalence of infection with human papillomavirus in females: a global review. J Adolesc Health. 2008;43(Suppl. 4):S5–25.
    1. Safaeian M, Kiddugavu M, Gravitt PE, Gange SJ, Ssekasanvu J, Murokora D, Sklar M, Serwadda D, Wawer MJ, Shah KV, Gray R. Determinants of Incidence and Clearance of High-Risk Human Papillomavirus Infections in Rural Rakai, Uganda. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1300–7. doi: 10.1158/1055-9965.EPI-07-2678.
    1. Banura C, Sandin S, van Doorn LJ, Quint W, Kleter B, Wabwire-Mangen F, Mbidde EK, Weiderpass E. Type-specific incidence, clearance and predictors of cervical human papillomavirus infections (HPV) among young women: a prospective study in Uganda. Infectious Agents and Cancer. 2010;5:7. doi: 10.1186/1750-9378-5-7.
    1. Namujju PB, Surcel HM, Kirnbauer R, Kaasila M, Banura C, Byaruhanga R, Muwanga M, Mbidde EK, Koskela P, Lehtinen M. Risk of being seropositive for multiple human papillomavirus types among Finnish and Ugandan women. Scand J Infect Dis. 2010;42(6-7):522–6. doi: 10.3109/00365540903582426.
    1. Newton R, Bousarghin L, Ziegler J, Casabonne D, Beral V, Mbidde E, Carpenter L, Parkin DM, Wabinga H, Mbulaiteye S, Jaffe H, Touzé A, Coursaget P. Uganda Kaposi's Sarcoma Study Group. Human papillomaviruses and cancer in Uganda. Eur J Cancer Prev. 2004;13(2):113–8.
    1. Clifford G, Franceschi S. HPV in Sub Saharan Africa. Papillomavirus Report. 2005;16:322–6. doi: 10.1179/095741905X49089.
    1. de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, Bosch FX. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007;7(7):453–9. doi: 10.1016/S1473-3099(07)70158-5.
    1. Frazer IH. Chapter 8: HPV Vaccines. Int J Gynecol & Obst. 2006;94(Suppl 1):S81–S88.
    1. Koutsky LA, Harper DM. Chapter 13: Current findings from prophylactic HPV vaccine trials. Vaccine. 2006;24(Suppl 3):S3/114–S3/121.
    1. Hildesheim A, Wang SS. Host and viral genetics and risk of cervical cancer: a review. Virus Res. 2002;89:229–40. doi: 10.1016/S0168-1702(02)00191-0.
    1. Moscicki AB, Schiffman M, Kjaer S, Villa LL. Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine. 2006;24(Suppl 3):S3/42–51.
    1. UNAIDS. UNGASS Country Progress Report.
    1. De Vuyst H, Lillo F, Broutet N, Smith JS. HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy. Eur J Cancer Prev. 2008;17(6):545–54. doi: 10.1097/CEJ.0b013e3282f75ea1.
    1. Parham GP, Mwanahamuntu MH, Sahasrabuddhe VV, Westfall AO, King KE, Chibwesha C, Pfaendler KS, Mkumba G, Mudenda V, Kapambwe S, Vermund SH, Hicks ML, Stringer JSA, Chi BH. Implementation of cervical cancer prevention services for HIV-infected women in Zambia: measuring program effectiveness. HIV Ther. 2010;4(6):713–22. doi: 10.2217/hiv.10.52.
    1. Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A. the IMPAACT P1047 Protocol Team. Safety and Immunogenicity of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine in HIV-Infected Children 7 to 12 Years Old. J Acquir Immune Defic Syndr. 2010;55(2):197–204. doi: 10.1097/QAI.0b013e3181de8d26.
    1. De Vuyst H, Gichangi P, Estambale B, Njuguna E, Franceschi S, Temmerman M. Human papillomavirus types in women with invasive cervical carcinoma by HIV status in Kenya. Int J Cancer. 2008;122(1):244–6. doi: 10.1002/ijc.23045.
    1. Louie KS, de Sanjosé S, Mayaud P. Epidemiology and prevention of human papillomavirus and cervical cancer in sub-Saharan Africa: a comprehensive review. Trop Med Int Health. 2009;14(10):1287–302. doi: 10.1111/j.1365-3156.2009.02372.x.
    1. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchner H, Castellsagué X, Teixeira JC, Skinner SK, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WAJ, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G. the HPV PATRICIA STUDY GROUP. Efficacy of human papillomavirus (HPV)-16/18AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA):final analysis of a double-blind, randomised study in young girls. Lancet. 2009;374(9686):301–14. doi: 10.1016/S0140-6736(09)61248-4.
    1. McPartland TS, Weaver BA, Lee SK, Koutsky LA. Men's perceptions and knowledge of human papillomavirus (HPV) infection and cervical cancer. J Am Coll Health. 2005;53(5):225–30. doi: 10.3200/JACH.53.5.225-230.
    1. Skegg DC, Corwin PA, Paul C, Doll R. Importance of the male factor in cancer of the cervix. Lancet. 1982;2(8298):581–3.
    1. Bosch FX, Castellsague X, Munoz N, de Sanjose S, Ghaffari AM, Gonzlez LC, Gili M, Izarzugaza I, Viladiu P, Navarro C, Vergara A, Ascunce N, Guerrero E, Keerti V, Shah KV. Male Sexual Behavior and Human Papillomavirus DNA: Key Risk Factors for Cervical Cancer in Spain. J Natl Cancer Inst. 1996;88:1060–7. doi: 10.1093/jnci/88.15.1060.
    1. Castellsagué X, Bosch FX, Muñoz N, Meijer CJLM, Shah KV, de Sanjosé S, Eluf-Neto J, Ngelangel CA, Chichareon S, Smith JS, Herrero R, Moreno V, Franceschi S. the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Male Circumcision, Penile Human Papillomavirus Infection, and Cervical Cancer in Female Partners. N Engl J Med. 2002;346:1105–1112. doi: 10.1056/NEJMoa011688.
    1. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D. Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males. N Engl J Med. 2011;364:401–411. doi: 10.1056/NEJMoa0909537.
    1. Garnett GP. Role of herd immunity in determining the effect of vaccines against sexually transmitted disease. J Infect Dis. 2005;191(Suppl 1):S97–S106.
    1. GOU. Approved budget estimates FY 2010/2011 Volume 1: Central Government Votes. Kampala. 2010.
    1. OAU. Abuja declaration on HIV/AIDS, Tuberculosis and other related infectious diseases. Abuja. 2001.
    1. GAVI Alliance. Vaccine Investiment Strategy. 2008.
    1. WHO. Position Paper: Human papillomavirus vaccines.
    1. Lorincz AT. In: HPV testing by hybrid capture. Emerging Issues of HPV Infections: From Science to Practice. Monsonego J, editor. Basel: Karger; 2006. pp. 54–62.
    1. Serwadda D, Wawer MJ, Shah KV, Sewankambo NK, Daniel R, Li C, Lorincz A, Meehan MP, Wabwire-Mangen F, Gray RH. Use of a Hybrid Capture Assay of self-collected vaginal swabs in rural Uganda for detection of human papillomavirus. J Infect Dis. 1999;180(4):1316–9. doi: 10.1086/315026.
    1. Safaeian M, Kiddugave M, Gravitt PE, Ssekasanvu J, Murokora D, Sklar M, Serwadda D, Wawer MJ, Shah KV, Gray R. Comparability of self-collected vaginal swabs and physcian collected cervical swabs for detection of human papillomavirus infections in Rakai, Uganda. Sex Transm Dis. 2007;34(7):429–36.
    1. Buonaguro FM, Tornesello ML, Salatiello I, Okong P, Buonaguro L, Beth-Giraldo E, Biryahwaho B, Sempala SD, Giraldo G. The Uganda study on HPV variants and genital cancers. J Clin Virol. 2000;19(1-2):31–41. doi: 10.1016/S1386-6532(00)00131-1.
    1. Schmauz R, Okong P, de Villiers EM, Dennin R, Brade L, Lwanga SK, Owor R. Multiple infections in cases of cervical cancer from a high-incidence area in tropic Africa. Int J Cancer. 1989;43(5):805–9. doi: 10.1002/ijc.2910430511.
    1. Odida M, de Sanjosé S, Quint W, Bosch FX, Klaustermeier J, Weiderpass E. Human Papillomavirus type distribution in invasive cervical cancer in Uganda. BMC Infect Dis. 2008;8:85. doi: 10.1186/1471-2334-8-85.
    1. Odida M, de Sanjosé S, Sandin S, Quiros B, Alemany L, Lloveras B, Quint W, Kleter B, Alejo M, van Doorn LJ, Weiderpass E. Comparison of human papillomavirus detection between freshly frozen tissue and paraffin embedded tissue of invasive cervical cancer. Infect Agent Cancer. 2010;5:15. doi: 10.1186/1750-9378-5-15.
    1. Tobian AR, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, Charvat B, Ssempijja V, Riedesel M, Oliver AE, Nowak RG, Moulton LH, Chen MZ, Reynolds SJ, Wawer MJ, Gray RH. Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis. N Engl J Med. 2009;360:1298–1309. doi: 10.1056/NEJMoa0802556.
    1. Serwadda D, Wawer MJ, Makumbi F, Kong X, Kigozi G, Gravitt P, Watya S, Nalugoda F, Ssempijja V, Tobian AAR, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Oliver ME, Iga B, Laeyendecker O, Gray RH. Circumcision of HIV-infected men: Effects on High Risk Human Papillomavirus Infections in a Randomized Trial in Rakai, Uganda. J Infect Dis. 2010;201(10):1463–9. doi: 10.1086/652185.
    1. Gray RH, Serwadda D, Kong X, Makumbi F, Kigozi G, Gravitt PE, Watya S, Nalugoda F, Ssempijja V, Tobian AA, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Iga B, Laeyendecker O, Oliver AE, Wawer MJ. Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201(10):1455–62. doi: 10.1086/652184.

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