Skip to main content
Book cover

HIV/AIDS-Associated Viral Oncogenesis pp 183–209Cite as

HPV-Associated Anal Cancer in the HIV/AIDS Patient

Part of the Cancer Treatment and Research book series (CTAR,volume 177)

Abstract

The prevalence of anal human papillomavirus (HPV) infection and anal high-grade squamous intraepithelial lesion (HSIL) remain high among HIV-infected individuals on effective antiretroviral therapy (ART). The incidence of HPV-related anal cancers has continued to increase since the introduction of ART. Therefore, ART may confer only limited benefit with respect to reducing the risk of anal HSIL and cancer. Efforts are in progress to define the efficacy of secondary prevention programs for prevention of anal cancer. In the modern ART era, anal cancer recurrence and survival outcomes are similar in HIV-infected and HIV-uninfected patients, but HIV-infected patients may experience more toxicities. This article reviews the current literature on HPV-associated anal cancer in the HIV-infected population, including epidemiology, screening, clinical characteristics, and treatment outcomes.

Keywords

  • HPV
  • Anal cancer
  • HIV
  • Immunosuppression
  • Vaccination

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-030-03502-0_7
  • Chapter length: 27 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   139.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-03502-0
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Hardcover Book
USD   179.99
Price excludes VAT (USA)
Learn about institutional subscriptions
Fig. 7.1
Fig. 7.2
Fig. 7.3

References

  1. Antiretroviral Therapy, Cohort C (2017) Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV

    Google Scholar 

  2. Goncalves PH et al (2016) Cancer prevention in HIV-infected populations. Semin Oncol 43(1):173–188

    CrossRef  PubMed  Google Scholar 

  3. Shiels MS et al (2011) Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 103(9):753–762

    CrossRef  PubMed  PubMed Central  Google Scholar 

  4. Bonnet F et al (2009) Changes in cancer mortality among HIV-infected patients: the Mortalite 2005 survey. Clin Infect Dis 48(5):633–639

    CrossRef  PubMed  Google Scholar 

  5. Silverberg MJ, Abrams DI (2007) AIDS-defining and non-AIDS-defining malignancies: cancer occurrence in the antiretroviral therapy era. Curr Opin Oncol 19(5):446–451

    PubMed  Google Scholar 

  6. Silverberg MJ et al (2012) Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis 54(7):1026–1034

    CrossRef  PubMed  PubMed Central  Google Scholar 

  7. Arbyn M et al (2012) EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease. Int J Cancer 131(9):1969–1982

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  8. de Martel C et al (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13(6):607–615

    CrossRef  PubMed  Google Scholar 

  9. Brickman C, Palefsky JM (2015) Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era. Curr HIV/AIDS Rep 12(1):6–15

    CrossRef  PubMed  Google Scholar 

  10. Hamid NA, Brown C, Gaston K (2009) The regulation of cell proliferation by the papillomavirus early proteins. Cell Mol Life Sci 66(10):1700–1717

    CAS  CrossRef  PubMed  Google Scholar 

  11. Munoz N et al (2006) Chapter 1: HPV in the etiology of human cancer. Vaccine 24(Suppl 3):S3/1-10

    CrossRef  CAS  Google Scholar 

  12. Bosch X, Harper D (2006) Prevention strategies of cervical cancer in the HPV vaccine era. Gynecol Oncol 103(1):21–24

    CrossRef  PubMed  Google Scholar 

  13. Frega A et al (2002) Giant condyloma acuminatum or buschke-Lowenstein tumor: review of the literature and report of three cases treated by CO2 laser surgery. A long-term follow-up. Anticancer Res 22(2B):1201–1204

    PubMed  Google Scholar 

  14. Machalek DA et al (2012) Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 13(5):487–500

    CrossRef  PubMed  Google Scholar 

  15. Robbins HA et al (2015) Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst 107(4)

    Google Scholar 

  16. Ellerbrock TV et al (2000) Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA 283(8):1031–1037

    CAS  CrossRef  PubMed  Google Scholar 

  17. Conley L et al (2010) Factors associated with prevalent abnormal anal cytology in a large cohort of HIV-infected adults in the United States. J Infect Dis 202(10):1567–1576

    CAS  CrossRef  PubMed  Google Scholar 

  18. Hessol NA et al (2013) Concomitant anal and cervical human papillomavirus infections and intraepithelial neoplasia in HIV-infected and uninfected women. AIDS 27(11):1743–1751

    CrossRef  PubMed  Google Scholar 

  19. Simpson S Jr et al (2016) Front-to-back & dabbing wiping behaviour post-toilet associated with anal neoplasia & HR-HPV carriage in women with previous HPV-mediated gynaecological neoplasia. Cancer Epidemiol 42:124–132

    CrossRef  PubMed  Google Scholar 

  20. Williams AB et al (1994) Anal and cervical human papillomavirus infection and risk of anal and cervical epithelial abnormalities in human immunodeficiency virus-infected women. Obstet Gynecol 83(2):205–211

    CAS  PubMed  Google Scholar 

  21. Darragh TM et al (2013) The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 32(1):76–115

    CrossRef  PubMed  Google Scholar 

  22. Darragh TM (2015) The LAST project and the diagnostic bottom line. Cytopathology 26(6):343–345

    CAS  CrossRef  PubMed  Google Scholar 

  23. D’Souza G et al (2016) Anal cancer screening in men who have sex with men in the multicenter AIDS Cohort study. J Acquir Immune Defic Syndr 71(5):570–576

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hernandez AL et al (2014) Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM. AIDS 28(9):1341–1349

    CrossRef  PubMed  Google Scholar 

  25. Palefsky JM et al (1998) Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 17(4):314–319

    CAS  CrossRef  PubMed  Google Scholar 

  26. Libois A et al (2017) Prolonged antiretroviral therapy is associated with fewer anal high-grade squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study. Sex Transm Infect 93(1):15–17

    CrossRef  PubMed  Google Scholar 

  27. van der Snoek EM et al (2012) Use of highly active antiretroviral therapy is associated with lower prevalence of anal intraepithelial neoplastic lesions and lower prevalence of human papillomavirus in HIV-infected men who have sex with men. Sex Transm Dis 39(7):495–500

    CrossRef  CAS  PubMed  Google Scholar 

  28. Hessol NA et al (2009) Anal intraepithelial neoplasia in a multisite study of HIV-infected and high-risk HIV-uninfected women. AIDS 23(1):59–70

    CrossRef  PubMed  Google Scholar 

  29. Stier EALJYLS, Jay N, Berry-Lawhorn JM, Einstein M, Palefsky JM, Wilkin T, Goldstone S, Chiao E (2016) Anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive (HIV+) women, prevalence and risk factors: AIDS malignancy consortium (AMC) 084. In: International anal neoplasia society (IANS) scientific meeting. San Francisoca, CA

    Google Scholar 

  30. Ahdieh L et al (2001) Prevalence, incidence, and type-specific persistence of human papillomavirus in human immunodeficiency virus (HIV)-positive and HIV-negative women. J Infect Dis 184(6):682–690

    CAS  CrossRef  PubMed  Google Scholar 

  31. Sun XW et al (1997) Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med 337(19):1343–1349

    CAS  CrossRef  PubMed  Google Scholar 

  32. Lillo FB et al (2001) Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy. J Infect Dis 184(5):547–551

    CAS  CrossRef  PubMed  Google Scholar 

  33. Paramsothy P et al (2009) The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology. Obstet Gynecol 113(1):26–31

    CrossRef  PubMed  Google Scholar 

  34. Blitz S et al (2013) Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women. J Infect Dis 208(3):454–462

    CAS  CrossRef  PubMed  Google Scholar 

  35. Konopnicki D et al (2013) Sustained viral suppression and higher CD4+ T-cell count reduces the risk of persistent cervical high-risk human papillomavirus infection in HIV-positive women. J Infect Dis 207(11):1723–1729

    CAS  CrossRef  PubMed  Google Scholar 

  36. Minkoff H et al (2010) Influence of adherent and effective antiretroviral therapy use on human papillomavirus infection and squamous intraepithelial lesions in human immunodeficiency virus-positive women. J Infect Dis 201(5):681–690

    CrossRef  PubMed  Google Scholar 

  37. Berry JM et al (2014) Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer 134(5):1147–1155

    CAS  CrossRef  PubMed  Google Scholar 

  38. Cachay E, Agmas W, Mathews C (2015) Five-year cumulative incidence of invasive anal cancer among HIV-infected patients according to baseline anal cytology results: an inception cohort analysis. HIV Med 16(3):191–195

    CAS  CrossRef  PubMed  Google Scholar 

  39. Mathews WC et al (2014) Natural history of anal dysplasia in an HIV-infected clinical care cohort: estimates using multi-state Markov modeling. PLoS ONE 9(8):e104116

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dalla Pria A et al (2014) High-resolution anoscopy screening of HIV-positive MSM: longitudinal results from a pilot study. AIDS 28(6):861–867

    CrossRef  PubMed  Google Scholar 

  41. McCredie MR et al (2008) Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9(5):425–434

    CrossRef  PubMed  Google Scholar 

  42. Kreimer AR et al (2011) Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the costa rica vaccine trial. Lancet Oncol 12(9):862–870

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  43. Palefsky JM et al (2011) HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 365(17):1576–1585

    CAS  CrossRef  PubMed  Google Scholar 

  44. Wilkin T et al (2010) Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis 202(8):1246–1253

    CrossRef  PubMed  Google Scholar 

  45. AIDS Malignancy Consortium (2016) Vaccine therapy in preventing human papillomavirus infection in young HIV-positive male patients who have sex with males. clinicaltrials.gov [Internet] [cited 2016 March 18]. Available from: https://clinicaltrials.gov/ct2/show/NCT01209325

  46. Deshmukh AA et al (2015) Long-term outcomes of adding HPV vaccine to the anal intraepithelial neoplasia treatment regimen in HIV-positive men who have sex with men. Clin Infect Dis 61(10):1527–1535

    CrossRef  PubMed  PubMed Central  Google Scholar 

  47. Joura EA et al (2015) A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 372(8):711–723

    CAS  CrossRef  PubMed  Google Scholar 

  48. Markowitz LE et al (2014) Human papillomavirus vaccination: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 63(RR-05):1–30

    Google Scholar 

  49. Sankaranarayanan R et al (2016) Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol 17(1):67–77

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  50. D’Addario M et al (2017) Two-dose schedules for human papillomavirus vaccine: systematic review and meta-analysis. Vaccine 35(22):2892–2901

    CrossRef  PubMed  Google Scholar 

  51. Meites E, Kempe A, Markowitz LE (2016) Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 65(49):1405–1408

    CrossRef  PubMed  Google Scholar 

  52. Sharma R et al (2013) Prevalence and risk factors for neutralizing antibodies to human papillomavirus types 16 and 18 in HIV-positive men who have sex with men. J Acquir Immune Defic Syndr 64(5):479–487

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  53. Walker TY et al (2017) National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 Years—United States, 2016. MMWR Morb Mortal Wkly Rep 66(33):874–882

    CrossRef  PubMed  PubMed Central  Google Scholar 

  54. AIDS Malignancy Consortium (2016) Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions. clinicaltrials.gov [Internet] [cited 2016 March 18]. Available from: https://clinicaltrials.gov/show/NCT02135419

  55. New York State Department of Health AI (2017) Anal dysplasia and cancer guideline. Accessed 1 June 2017. Available from: http://www.hivguidelines.org/

  56. Aberg JA et al (2014) Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the infectious diseases society of America. Clin Infect Dis 58(1):1–10

    CrossRef  PubMed  Google Scholar 

  57. Goldie SJ et al (1999) The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in homosexual and bisexual HIV-positive men. JAMA 281(19):1822–1829

    CAS  CrossRef  PubMed  Google Scholar 

  58. Uronis HE, Bendell JC (2007) Anal cancer: an overview. Oncologist 12(5):524–534

    CrossRef  PubMed  Google Scholar 

  59. Sawaya GF, Huchko MJ (2017) Cervical cancer screening. Med Clin North Am 101(4):743–753

    CrossRef  PubMed  PubMed Central  Google Scholar 

  60. Arbyn M et al (2012) Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 30(Suppl 5):F88–F99

    CrossRef  PubMed  Google Scholar 

  61. Burgos J et al (2017) The role of oncogenic HPV determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM. AIDS

    Google Scholar 

  62. Hidalgo-Tenorio C et al (2015) The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males. PLoS One 10(4):e0123590

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  63. Salit IE et al (2010) The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening. AIDS 24(9):1307–1313

    PubMed  Google Scholar 

  64. Berry JM et al (2009) Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia. Dis Colon Rectum 52(2):239–247

    CrossRef  PubMed  Google Scholar 

  65. Goldstone SE, Enyinna CS, Davis TW (2009) Detection of oncogenic human papillomavirus and other predictors of anal high-grade dysplasia in men who have sex with men with abnormal cytology. Dis Colon Rectum 52(1):31–39

    CrossRef  PubMed  Google Scholar 

  66. Stier EA, Chigurupati NL, Fung L (2016) Prophylactic HPV vaccination and anal cancer. Hum Vaccin Immunother

    Google Scholar 

  67. Ryan DP, Compton CC, Mayer RJ (2000) Carcinoma of the anal canal. N Engl J Med 342(11):792–800

    CAS  CrossRef  PubMed  Google Scholar 

  68. Klas JV et al (1999) Malignant tumors of the anal canal: the spectrum of disease, treatment, and outcomes. Cancer 85(8):1686–1693

    CAS  CrossRef  PubMed  Google Scholar 

  69. Touboul E et al (1994) Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients. Cancer 73(6):1569–1579

    CAS  CrossRef  PubMed  Google Scholar 

  70. Jemal A et al (2013) Annual report to the nation on the status of cancer, 1975–2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 105(3):175–201

    CrossRef  PubMed  PubMed Central  Google Scholar 

  71. Shiels MS et al (2015) Anal cancer incidence in the United States, 1977–2011: distinct patterns by histology and behavior. Cancer Epidemiol Biomarkers Prev 24(10):1548–1556

    CrossRef  PubMed  PubMed Central  Google Scholar 

  72. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30

    CrossRef  PubMed  Google Scholar 

  73. UNAIDS, Fact Sheet 2015 (2015) http://www.unaids.org/en/resources/campaigns/HowAIDSchangedeverything/factsheet

  74. Control CFD (2015) HIIV in the United States: at a glance. http://www.cdc.gov/hiv/statistics/overview/ataglance.html

  75. Shiels MS et al (2012) Impact of the HIV epidemic on the incidence rates of anal cancer in the United States. J Natl Cancer Inst 104(20):1591–1598

    CrossRef  PubMed  PubMed Central  Google Scholar 

  76. Frisch M, Biggar RJ, Goedert JJ (2000) Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 92(18):1500–1510

    CAS  CrossRef  PubMed  Google Scholar 

  77. Reekie J et al (2010) Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies. Cancer 116(22):5306–5315

    CrossRef  PubMed  Google Scholar 

  78. Silverberg MJ et al (2015) Cumulative incidence of cancer among persons with HIV in North America: a Cohort study. Ann Intern Med 163(7):507–518

    CrossRef  PubMed  PubMed Central  Google Scholar 

  79. Engels EA et al (2011) Use of surveillance, epidemiology, and end results-medicare data to conduct case-control studies of cancer among the US elderly. Am J Epidemiol 174(7):860–870

    CrossRef  PubMed  PubMed Central  Google Scholar 

  80. Yanik EL, Katki HA, Engels EA (2016) Cancer risk among the HIV-infected elderly in the United States. AIDS 30(10):1663–1668

    CrossRef  PubMed  Google Scholar 

  81. Guiguet M et al (2009) Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol 10(12):1152–1159

    CAS  CrossRef  PubMed  Google Scholar 

  82. Powles T et al (2009) Highly active antiretroviral therapy and the incidence of non-AIDS-defining cancers in people with HIV infection. J Clin Oncol 27(6):884–890

    CrossRef  PubMed  Google Scholar 

  83. Silverberg MJ et al (2011) HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev 20(12):2551–2559

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  84. Barillari G et al (2012) Ritonavir or saquinavir impairs the invasion of cervical intraepithelial neoplasia cells via a reduction of MMP expression and activity. AIDS 26(8):909–919

    CAS  CrossRef  PubMed  Google Scholar 

  85. Toschi E et al (2011) Human immunodeficiency virus protease inhibitors reduce the growth of human tumors via a proteasome-independent block of angiogenesis and matrix metalloproteinases. Int J Cancer 128(1):82–93

    CAS  CrossRef  PubMed  Google Scholar 

  86. Gupta AK et al (2007) The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response. Neoplasia 9(4):271–278

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  87. UKCCCR Anal Cancer Trial Working Party (1996) Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UK Co-ordinating Committee on Cancer Research. Lancet 348(9034):1049–1054

    Google Scholar 

  88. Ajani JA et al (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299(16):1914–1921

    CAS  CrossRef  PubMed  Google Scholar 

  89. Flam M et al (1996) Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14(9):2527–2539

    CAS  CrossRef  PubMed  Google Scholar 

  90. Gunderson LL et al (2012) Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol 30(35):4344–4351

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  91. James RD et al (2013) Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol 14(6):516–524

    CAS  CrossRef  PubMed  Google Scholar 

  92. Northover J et al (2010) Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR anal cancer trial (ACT I). Br J Cancer 102(7):1123–1128

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  93. Peiffert D et al (2012) Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol 30(16):1941–1948

    CAS  CrossRef  PubMed  Google Scholar 

  94. Chuong MD et al (2013) Intensity-modulated radiation therapy vs. 3D conformal radiation therapy for squamous cell carcinoma of the anal canal. Gastrointest Cancer Res 6(2):39–45

    Google Scholar 

  95. Kachnic LA et al (2013) RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 86(1):27–33

    CAS  CrossRef  PubMed  Google Scholar 

  96. Chadha M et al (1994) Squamous-cell carcinoma of the anus in HIV-positive patients. Dis Colon Rectum 37(9):861–865

    CAS  CrossRef  PubMed  Google Scholar 

  97. Peddada AV et al (1997) Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 37(5):1101–1105

    CAS  CrossRef  PubMed  Google Scholar 

  98. Kim JH et al (2001) HIV-positive patients with anal carcinoma have poorer treatment tolerance and outcome than HIV-negative patients. Dis Colon Rectum 44(10):1496–1502

    CAS  CrossRef  PubMed  Google Scholar 

  99. Place RJ et al (2001) Outcome analysis of HIV-positive patients with anal squamous cell carcinoma. Dis Colon Rectum 44(4):506–512

    CAS  CrossRef  PubMed  Google Scholar 

  100. Hoffman R et al (1999) The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 44(1):127–131

    CAS  CrossRef  PubMed  Google Scholar 

  101. Holland JM, Swift PS (1994) Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy. Radiology 193(1):251–254

    CAS  CrossRef  PubMed  Google Scholar 

  102. Blazy A et al (2005) Anal carcinomas in HIV-positive patients: high-dose chemoradiotherapy is feasible in the era of highly active antiretroviral therapy. Dis Colon Rectum 48(6):1176–1181

    CrossRef  PubMed  Google Scholar 

  103. Alfa-Wali M et al (2012) Chemoradiotherapy for anal cancer in HIV patients causes prolonged CD4 cell count suppression. Ann Oncol 23(1):141–147

    CAS  CrossRef  PubMed  Google Scholar 

  104. Chiao EY et al (2008) Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 26(3):474–479

    CrossRef  PubMed  Google Scholar 

  105. Fraunholz I et al (2011) Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy? Radiother Oncol 98(1):99–104

    CAS  CrossRef  PubMed  Google Scholar 

  106. Seo Y et al (2009) Outcomes of chemoradiotherapy with 5-Fluorouracil and mitomycin C for anal cancer in immunocompetent versus immunodeficient patients. Int J Radiat Oncol Biol Phys 75(1):143–149

    CAS  CrossRef  PubMed  Google Scholar 

  107. Wexler A et al (2008) Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy. Dis Colon Rectum 51(1):73–81

    CrossRef  PubMed  Google Scholar 

  108. Martin D et al (2017) Are there HIV-specific differences for anal cancer patients treated with standard chemoradiotherapy in the era of combined antiretroviral therapy? Clin Oncol (R Coll Radiol) 29(4):248–255

    CAS  CrossRef  Google Scholar 

  109. Sparano JA et al (2017) Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma: a phase II AIDS malignancy consortium trial. J Clin Oncol 35(7):727–733

    CAS  CrossRef  PubMed  Google Scholar 

  110. Hogg ME et al (2009) HIV and anal cancer outcomes: a single institution’s experience. Dis Colon Rectum 52(5):891–897

    CrossRef  PubMed  Google Scholar 

  111. Munoz-Bongrand N et al (2011) Anal carcinoma in HIV-infected patients in the era of antiretroviral therapy: a comparative study. Dis Colon Rectum 54(6):729–735

    CrossRef  PubMed  Google Scholar 

  112. Oehler-Janne C et al (2008) HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. J Clin Oncol 26(15):2550–2557

    CrossRef  PubMed  Google Scholar 

  113. Meyer JE et al (2013) HIV positivity but not HPV/p16 status is associated with higher recurrence rate in anal cancer. J Gastrointest Cancer 44(4):450–455

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  114. Grew D et al (2015) HIV infection is associated with poor outcomes for patients with anal cancer in the highly active antiretroviral therapy era. Dis Colon Rectum 58(12):1130–1136

    CrossRef  PubMed  Google Scholar 

  115. Meulendijks D et al (2014) Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J Cancer 111(9):1726–1733

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  116. Goodman KA et al (2014) Capecitabine plus mitomycin in patients undergoing definitive chemoradiation for anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 90:S32–S33

    CrossRef  Google Scholar 

  117. Oliveira SC et al (2016) Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal. J Gastrointest Cancer 47(1):75–81

    CAS  CrossRef  PubMed  Google Scholar 

  118. Van Damme N et al (2010) Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas. BMC Cancer 10:189

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bonner JA et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–578

    CAS  CrossRef  PubMed  Google Scholar 

  120. Bonner JA et al (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11(1):21–28

    CAS  CrossRef  PubMed  Google Scholar 

  121. Burtness B et al (2005) Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern cooperative oncology group study. J Clin Oncol 23(34):8646–8654

    CrossRef  PubMed  Google Scholar 

  122. Deutsch E et al (2013) Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial. Ann Oncol 24(11):2834–2838

    CAS  CrossRef  PubMed  Google Scholar 

  123. Levy A et al (2015) Low response rate after cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: long-term results of the UNICANCER ACCORD 16 phase II trial. Radiother Oncol 114(3):415–416

    CrossRef  PubMed  Google Scholar 

  124. Garg M, Lee JY, Kachnic LA, Catalano PJ, Henry DH, Cooley TP, Ratner L, Wachsman W, Aboulafia DM, Benson AB, Palefsky J, Whittington R, Mitsuyasu RT, Sparano JA (2012) Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5fluorouracil (5FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIVpositive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): Safety and preliminary efficacy results. J Clin Oncol 30(suppl; abstr 4030)

    Google Scholar 

  125. Mullen JT et al (2007) Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol 14(2):478–483

    CrossRef  PubMed  Google Scholar 

  126. Schiller DE et al (2007) Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol 14(10):2780–2789

    CrossRef  PubMed  Google Scholar 

  127. Cummings BJ (2006) Metastatic anal cancer: the search for cure. Onkologie 29(1–2):5–6

    PubMed  Google Scholar 

  128. Eng C (2006) Anal cancer: current and future methodology. Cancer Invest 24(5):535–544

    CrossRef  PubMed  Google Scholar 

  129. Faivre C et al (1999) 5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer. Bull Cancer 86(10):861–865

    CAS  PubMed  Google Scholar 

  130. Freeman GJ et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  131. Ott PA et al (2017) Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol 28(5):1036–1041

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  132. Day CL et al (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443(7109):350–354

    CAS  CrossRef  PubMed  Google Scholar 

  133. Brahmer J et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  134. Ferris RL et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  135. Motzer RJ et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  136. Robert C et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330

    CAS  CrossRef  PubMed  Google Scholar 

  137. Morris VK et al (2017) Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol 18(4):446–453

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  138. Rudek MA, Flexner C, Ambinder RF (2011) Use of antineoplastic agents in patients with cancer who have HIV/AIDS. Lancet Oncol 12(9):905–912

    CrossRef  PubMed  PubMed Central  Google Scholar 

  139. Montoto S et al (2012) HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era. J Clin Oncol 30(33):4111–4116

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ratner L et al (2001) Chemotherapy for human immunodeficiency virus-associated non-Hodgkin’s lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 19(8):2171–2178

    CAS  CrossRef  PubMed  Google Scholar 

  141. Vaccher E et al (2001) Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma. Cancer 91(1):155–163

    CAS  CrossRef  PubMed  Google Scholar 

  142. Gunthard HF et al (2014) Antiretroviral treatment of adult HIV infection: 2014 recommendations of the international antiviral society-USA panel. JAMA 312(4):410–425

    CrossRef  CAS  PubMed  Google Scholar 

  143. Margolis AM et al (2014) A review of the toxicity of HIV medications. J Med Toxicol 10(1):26–39

    CAS  CrossRef  PubMed  Google Scholar 

  144. Rudek MA et al (2014) A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus-positive patients with cancer: AIDS malignancy consortium trial AMC 061. Cancer 120(8):1194–1202

    CAS  CrossRef  PubMed  Google Scholar 

  145. Pajonk F et al (2002) The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells. Cancer Res 62(18):5230–5235

    CAS  PubMed  Google Scholar 

  146. Kesselring A et al (2011) Immunodeficiency as a risk factor for non-AIDS-defining malignancies in HIV-1-infected patients receiving combination antiretroviral therapy. Clin Infect Dis 52(12):1458–1465

    CAS  CrossRef  PubMed  Google Scholar 

  147. Hakim FT et al (1997) Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood 90(9):3789–3798

    CAS  PubMed  Google Scholar 

  148. Komada Y et al (1992) Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy. Cancer Immunol Immunother 35(4):271–276

    CAS  CrossRef  PubMed  Google Scholar 

  149. Sankatsing SU et al (2013) Prolonged decrease of CD4+ T lymphocytes in HIV-1-infected patients after radiotherapy for a solid tumor. J Acquir Immune Defic Syndr 62(5):546–549

    CrossRef  PubMed  Google Scholar 

  150. Bouma G, Strober W (2003) The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3(7):521–533

    CAS  CrossRef  PubMed  Google Scholar 

  151. Chun TW et al (1999) Effect of interleukin-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. Nat Med 5(6):651–655

    CAS  CrossRef  PubMed  Google Scholar 

  152. Bunn PA Jr et al (1995) Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13(7):1632–1641

    CrossRef  PubMed  Google Scholar 

  153. Fraunholz IB et al (2014) Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease. Dis Colon Rectum 57(4):423–431

    CrossRef  PubMed  Google Scholar 

  154. Kaplan JE et al (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58(RR-4):1–207; quiz CE1-4

    Google Scholar 

  155. Segal BH et al (2008) Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 6(2):122–174

    CrossRef  PubMed  Google Scholar 

  156. Crosbie EJ et al (2013) Human papillomavirus and cervical cancer. Lancet 382(9895):889–899

    CrossRef  PubMed  Google Scholar 

  157. Glynne-Jones R et al (2014) Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Radiother Oncol 111(3):330–339

    CrossRef  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Wang has no relevant disclosures.

Dr. Palefsky discloses that he is a member of a Merck scientific advisory board, and receives travel support form Merck. He receives travel and research grant support from Merck. He is a consultant to Ubiome, Agenovir, and Antiva Biosciences.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA

    Chia-Ching J. Wang

  2. Division of Infectious Diseases, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA

    Joel M. Palefsky

  3. 995 Potrero Avenue, Building 80, 4th Floor, San Francisco, CA, 94110, USA

    Chia-Ching J. Wang

  4. 513 Parnassus Ave, Med Sci Room 420E, Box 0654, San Francisco, CA, 94143, USA

    Joel M. Palefsky

Authors
  1. Chia-Ching J. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel M. Palefsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joel M. Palefsky .

Editor information

Editors and Affiliations

  1. Penn State Cancer Institute, Penn State University, Hershey, PA, USA

    MD Craig Meyers

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Wang, CC.J., Palefsky, J.M. (2019). HPV-Associated Anal Cancer in the HIV/AIDS Patient. In: Meyers, C. (eds) HIV/AIDS-Associated Viral Oncogenesis. Cancer Treatment and Research, vol 177. Springer, Cham. https://doi.org/10.1007/978-3-030-03502-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-03502-0_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-03501-3

  • Online ISBN: 978-3-030-03502-0

  • eBook Packages: MedicineMedicine (R0)