Uterine Cervical Cancer in Women with HIV Infection

  • Linda MileshkinEmail author
  • Evangeline Ponnusamy
  • Catherine Louise Cherry


This chapter discusses the high prevalence of human papilloma virus (HPV)-associated malignancies in patients with human immunodeficiency virus (HIV), leading to cervical cancer being designated as an acquired immune deficiency syndrome (AIDS)-defining condition. HIV infection is associated with an increased mortality in this group of patients. This is attributed to likely enhanced HPV carcinogenesis in the setting of HIV-related immunosuppression. There continues to be a high prevalence of cervical cancer in the developing world, where low rates of cervical cancer vaccination and Pap smear testing are reported, and this is especially more common in the HIV-infected cohort. There exist no robust guidelines for the treatment of locally advanced cervical cancer in women with HIV, although early initiation of combination antiretroviral therapy (cART) has been recommended and has led to better rates of treatment completion.


Cervical cancer and HIV HIV and cervical cancer HAART cART HPV and HIV AIDS and cervical cancer 


  1. 1.
    Arbyn M, Castellsague X, de Sanjose S, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol Off J Eur Soc Med Oncol. 2011;22(12):2675–86.CrossRefGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefGoogle Scholar
  3. 3.
    Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(14):2137–50.CrossRefGoogle Scholar
  4. 4.
    Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and morality worldwide. ARC CancerBase No. 11 [internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: Accessed 28 Aug 2017.
  5. 5.
    (CDC) CfDC. Pneumocystic pneumoniae – Los Angeles. MMWR Morb Mortal Wkly Rep. 1981;30(21):250–2.Google Scholar
  6. 6.
    Marx JL. Strong new candidate for AIDS agent. Science. 1984;224(4648):475–7.CrossRefGoogle Scholar
  7. 7.
    Case K. Nomenclature: human immunodeficiency virus. Ann Intern Med. 1986;105(1):133.CrossRefGoogle Scholar
  8. 8.
    Maiman M, Fruchter RG, Serur E, Remy JC, Feuer G, Boyce J. Human immunodeficiency virus infection and cervical neoplasia. Gynecol Oncol. 1990;38(3):377–82.CrossRefGoogle Scholar
  9. 9.
    Collier AC, Coombs RW, Schoenfeld DA, AIDS Clinical Trials Group, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. N Engl I Med. 1996;334(16):1011–7.CrossRefGoogle Scholar
  10. 10.
    D’Aquila RT, Hughes MD, Johnson VA, National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators, et al. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1996;124(12):1019–30.CrossRefGoogle Scholar
  11. 11.
    van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F, Anoc s. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010;24(10):1527–35.CrossRefGoogle Scholar
  12. 12.
    Mills EJ, Bakanda C, Birungi J, et al. Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda. Ann Intern Med. 2011;155(4):209–16.CrossRefGoogle Scholar
  13. 13.
    Group ISS, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795–807.CrossRefGoogle Scholar
  14. 14.
    Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS. 2014;28(4):453–65.CrossRefGoogle Scholar
  15. 15.
    Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97(6):425–32.CrossRefGoogle Scholar
  16. 16.
    Clifford GM, de Vuyst H, Tenet V, Plummer M, Tully S, Franceschi S. Effect of HIV infection on human papillomavirus types causing invasive cervical cancer in Africa. J Acquir Immune Defic Syndr. 2016;73(3):332–9.CrossRefGoogle Scholar
  17. 17.
    Dryden-Peterson S, Bvochora-Nsingo M, Suneja G, et al. HIV infection and survival among women with cervical cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(31):3749–57.CrossRefGoogle Scholar
  18. 18.
    Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA, Study HACM. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99(12):962–72.CrossRefGoogle Scholar
  19. 19.
    Ntekim A, Campbell O, Rothenbacher D. Optimal management of cervical cancer in HIV-positive patients: a systematic review. Cancer Med. 2015;4(9):1381–93.CrossRefGoogle Scholar
  20. 20.
    Zheng ZM, Baker CC. Papillomavirus genome structure, expression, and post-transcriptional regulation. Front Biosci. 2006;11:2286–302.CrossRefGoogle Scholar
  21. 21.
    Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–27.CrossRefGoogle Scholar
  22. 22.
    Munoz N, Hernandez-Suarez G, Mendez F, et al. Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women. Br J Cancer. 2009;100(7):1184–90.CrossRefGoogle Scholar
  23. 23.
    Ng’andwe C, Lowe JJ, Richards PJ, Hause L, Wood C, Angeletti PC. The distribution of sexually-transmitted human papillomaviruses in HIV positive and negative patients in Zambia, Africa. BMC Infect Dis. 2007;7:77.CrossRefGoogle Scholar
  24. 24.
    Darwich L, Canadas MP, Sirera G, et al. Human papillomavirus genotype distribution and human papillomavirus 16 and human papillomavirus 18 genomic integration in invasive and in situ cervical carcinoma in human immunodeficiency virus-infected women. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2011;21(8):1486–90.CrossRefGoogle Scholar
  25. 25.
    Tugizov SM, Herrera R, Chin-Hong P, et al. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus. Virology. 2013;446(1–2):378–88.CrossRefGoogle Scholar
  26. 26.
    Laurson J, Khan S, Chung R, Cross K, Raj K. Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis. 2010;31(5):918–26.CrossRefGoogle Scholar
  27. 27.
    Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. Accessed 02/09/2017.Google Scholar
  28. 28.
    Organisation WH. WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention2013. Accessed.
  29. 29.
    Lince-Deroche N, Phiri J, Michelow P, Smith JS, Firnhaber C. Costs and cost effectiveness of three approaches for cervical cancer screening among HIV-positive women in Johannesburg, South Africa. PLoS One. 2015;10(11):e0141969.CrossRefGoogle Scholar
  30. 30.
    WHO. Comprehensive cervical cancer control: a guide to essential practice. 2nd ed. Geneva: WHO Press; 2014.Google Scholar
  31. 31.
    Qiao L, Li B, Long M, Wang X, Wang A, Zhang G. Accuracy of visual inspection with acetic acid and with Lugol’s iodine for cervical cancer screening: meta-analysis. J Obstet Gynaecol Res. 2015;41(9):1313–25.CrossRefGoogle Scholar
  32. 32.
    Massad LS, Seaberg EC, Wright RL, et al. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstet Gynecol. 2008;111(6):1388–93.CrossRefGoogle Scholar
  33. 33.
    Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197(4):346–55.CrossRefGoogle Scholar
  34. 34.
    Ahdieh-Grant L, Li R, Levine AM, et al. Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2004;96(14):1070–6.CrossRefGoogle Scholar
  35. 35.
    Delmas MC, Larsen C, van Benthem B, European Study Group on Natural History of HIV Infection in Women, et al. Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. AIDS. 2000;14(12):1775–84.CrossRefGoogle Scholar
  36. 36.
    Brand A, Hammond I, Pather S, Roeske L, Wrede CD. Cancer council Australia cervical Cancer screening guidelines working party. 16. Screening in immune-deficient women. Accessed 1/9/2017.
  37. 37.
    Reimers LL, Sotardi S, Daniel D, et al. Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women. Gynecol Oncol. 2010;119(1):92–7.CrossRefGoogle Scholar
  38. 38.
    Heard I, Potard V, Foulot H, Chapron C, Costagliola D, Kazatchkine MD. High rate of recurrence of cervical intraepithelial neoplasia after surgery in HIV-positive women. J Acquir Immune Defic Syndr. 2005;39(4):412–8.CrossRefGoogle Scholar
  39. 39.
    Maiman M, Watts DH, Andersen J, Clax P, Merino M, Kendall MA. Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial. Obstet Gynecol. 1999;94(6):954–61.PubMedGoogle Scholar
  40. 40.
    Levin MJ, Moscicki AB, Song LY, et al. 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.CrossRefGoogle Scholar
  41. 41.
    Wilkin T, Lee JY, Lensing SY, et al. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis. 2010;202(8):1246–53.CrossRefGoogle Scholar
  42. 42.
    Marth C, Landoni F, Mahner S, et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(suppl_4):iv72–83.CrossRefGoogle Scholar
  43. 43.
    Gichangi P, Bwayo J, Estambale B, et al. HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer. Gynecol Oncol. 2006;100(2):405–11.CrossRefGoogle Scholar
  44. 44.
    Housri N, Yarchoan R, Kaushal A. Radiotherapy for patients with the human immunodeficiency virus: are special precautions necessary? Cancer. 2010;116(2):273–83.CrossRefGoogle Scholar
  45. 45.
    Ferreira MP, Coghill AE, Chaves CB, et al. Outcomes of cervical cancer among HIV-infected and HIV-uninfected women treated at the Brazilian National Institute of Cancer. AIDS. 2017;31(4):523–31.CrossRefGoogle Scholar
  46. 46.
    Datta NR, Samiei M, Bodis S. Radiation therapy infrastructure and human resources in low- and middle-income countries: present status and projections for 2020. Int J Radiat Oncol Biol Phys. 2014;89(3):448–57.CrossRefGoogle Scholar
  47. 47.
    Chuang LT, Temin S, Camacho R, et al. Management and care of women with invasive cervical cancer: American Society of Clinical Oncology resource-stratified clinical practice guideline. J Glob Oncol. 2016;2(5):311–40.CrossRefGoogle Scholar
  48. 48.
    Sebastiao AM, da Silva Rocha LS, Gimenez RD, et al. Carboplatin-based chemoradiotherapy in advanced cervical cancer: an alternative to cisplatin-based regimen? Eur J Obstet Gynecol Reprod Biol. 2016;201:161–5.CrossRefGoogle Scholar
  49. 49.
    Au-Yeung G, Mileshkin L, Bernshaw DM, Kondalsamy-Chennakesavan S, Rischin D, Narayan K. Radiation with cisplatin or carboplatin for locally advanced cervix cancer: the experience of a tertiary cancer centre. J Med Imaging Radiat Oncol. 2013;57(1):97–104.CrossRefGoogle Scholar
  50. 50.
    Simonds HM, Wright JD, du Toit N, Neugut AI, Jacobson JS. Completion of and early response to chemoradiation among human immunodeficiency virus (HIV)-positive and HIV-negative patients with locally advanced cervical carcinoma in South Africa. Cancer. 2012;118(11):2971–9.CrossRefGoogle Scholar
  51. 51.
    Simonds HM, Neugut AI, Jacobson JS. HIV status and acute hematologic toxicity among patients with cervix cancer undergoing radical chemoradiation. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2015;25(5):884–90.CrossRefGoogle Scholar
  52. 52.
    Rudek MA, Flexner C, Ambinder RF. Use of antineoplastic agents in patients with cancer who have HIV/AIDS. Lancet Oncol. 2011;12(9):905–12.CrossRefGoogle Scholar
  53. 53.
    Uldrick TS, Wyvill KM, Kumar P, et al. Phase II study of bevacizumab in patients with HIV-associated Kaposi’s sarcoma receiving antiretroviral therapy. J Clin Oncology Off J Am Soc Clin Oncol. 2012;30(13):1476–83.CrossRefGoogle Scholar
  54. 54.
    Cherry CL, Wadley AL, Kamerman PR. Painful HIV-associated sensory neuropathy. Pain Manag. 2012;2(6):543–52.CrossRefGoogle Scholar
  55. 55.
    Mahendra VS, Gilborn L, Bharat S, et al. Understanding and measuring AIDS-related stigma in health care settings: a developing country perspective. SAHARA J J Soc Asp HIV/AIDS Res Alliance. 2007;4(2):616–25.CrossRefGoogle Scholar
  56. 56.
    Rutledge SE, Abell N, Padmore J, McCann TJ. AIDS stigma in health services in the Eastern Caribbean. Sociol Health Illn. 2009;31(1):17–34.CrossRefGoogle Scholar
  57. 57.
    Cannon Poindexter C. HIV stigma and discrimination in medical settings: stories from African women in New Zealand. Soc Work Health Care. 2013;52(8):704–27.CrossRefGoogle Scholar
  58. 58.
    Stutterheim SE, Sicking L, Brands R, et al. Patient and provider perspectives on HIV and HIV-related stigma in Dutch health care settings. AIDS Patient Care STDs. 2014;28(12):652–65.CrossRefGoogle Scholar
  59. 59.
    Nyblade L, Stangl A, Weiss E, Ashburn K. Combating HIV stigma in health care settings: what works? J Int AIDS Soc. 2009;12:15.CrossRefGoogle Scholar
  60. 60.
    Li L, Wu Z, Liang LJ, et al. Reducing HIV-related stigma in health care settings: a randomized controlled trial in China. Am J Public Health. 2013;103(2):286–92.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Linda Mileshkin
    • 1
    Email author
  • Evangeline Ponnusamy
    • 1
  • Catherine Louise Cherry
    • 2
    • 3
    • 4
  1. 1.Department of Medical OncologyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Department of Infectious DiseasesMonash University and Alfred HealthMelbourneAustralia
  3. 3.Burnet InstituteMelbourneAustralia
  4. 4.Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa

Personalised recommendations