Vaccinations for Anal Squamous Cancer: Current and Emerging Therapies

Abstract

Human papillomavirus (HPV) infection is responsible for 4.3% of the global cancer burden. Since 2006, current HPV vaccines have reduced the prevalence of the virus in adolescent girls, reduced the prevalence of genital warts, and been proven to reduce the progression of anal intraepithelial neoplasia in men. Herein, we review the epidemiology, virology, and immunology behind the prophylactic HPV vaccines and current recommendations for its use. We also review future immune therapies being trialed for use against HPV-related cancers including anal cancer.

Keywords

anal cancer - human papillomavirus - anal intraepithelial neoplasia - anal squamous cell cancer

Disclosures

The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense, or the U.S. Government.

• References

• 1 Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/std/hpv/stdfact-hpv.htm . Accessed September 2018
• 2 McQuillan G, Kruszon-Moran D, Markowitz LE, Unger ER, Paulose-Ram R. Prevalence of HPV in adults aged 18-69: United States, 2011-2014. NCHS Data Brief 2017; 280 (280) 1-8
• 3 Centers for Disease Control and Prevention. Available at: www.cdc.gov/cancer/hpv/statistics/cases.htm#5
• 4 http://globocan.iarc.fr/Pages/fact_sheets_population.aspx . Accessed September 2018
• 5 Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006; 24 (Suppl 3): S3: 11-25
• 6 Mariani L, Venuti A. HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future. J Transl Med 2010; 8: 105
• 7 Brewster DH, Bhatti LA. Increasing incidence of squamous cell carcinoma of the anus in Scotland, 1975-2002. Br J Cancer 2006; 95 (01) 87-90
• 8 Palefsky JM, Rubin M. The epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin North Am 2009; 36 (01) 187-200
• 9 Hernandez BY, McDuffie K, Zhu X. , et al. Anal human papillomavirus infection in women and its relationship with cervical infection. Cancer Epidemiol Biomarkers Prev 2005; 14 (11, Pt 1): 2550-2556
• 10 Baldwin JI, Baldwin JD. Heterosexual anal intercourse: an understudied, high-risk sexual behavior. Arch Sex Behav 2000; 29 (04) 357-373
• 11 Nyitray A, Nielson CM, Harris RB. , et al. Prevalence of and risk factors for anal human papillomavirus infection in heterosexual men. J Infect Dis 2008; 197 (12) 1676-1684
• 12 Nyitray AG, da Silva RJ, Baggio ML. , et al. The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: the HIM study. Sex Transm Dis 2011; 38 (10) 932-940
• 13 Adami J, Gäbel H, Lindelöf B. , et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 2003; 89 (07) 1221-1227
• 14 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) 1500-1510
• 15 Piketty C, Selinger-Leneman H, Grabar S. , et al; FHDH-ANRS CO 4. Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy. AIDS 2008; 22 (10) 1203-1211
• 16 Libois A, Feoli F, Nkuize M. , et al. 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 2017; 93 (01) 15-17
• 17 Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 2010; 401 (01) 70-79
• 18 Doorbar J, Quint W, Banks L. , et al. The biology and life-cycle of human papillomaviruses. Vaccine 2012; 30 (Suppl 5): F55-F70
• 19 Stanley M. Immune responses to human papillomavirus. Vaccine 2006; 24 (Suppl 1): S16-S22
• 20 Bernard H-U, Calleja-Macias IE, Dunn ST. Genome variation of human papillomavirus types: phylogenetic and medical implications. Int J Cancer 2006; 118 (05) 1071-1076
• 21 Einstein MH, Schiller JT, Viscidi RP. , et al. Clinician's guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis 2009; 9 (06) 347-356
• 22 Food and Drug Administration. Product approval-prescribing information {Package insert}. Gardasil [human papillomavirus quadrivalent (type 6, 11, 16,18) vaccine, recombinant]. Merck & Co, Inc. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2014
• 23 Food and Drug Administration. Product approval-prescribing information {Package insert}. Cervarix [human papillomavirus bivalent (types 16,18) vaccine, recombinant]. Glaxo Smith Kline. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2014
• 24 Harper DM, Franco EL, Wheeler C. , et al; GlaxoSmithKline HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364 (9447): 1757-1765
• 25 Harper DM, Franco EL, Wheeler CM. , et al; HPV Vaccine Study group. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367 (9518): 1247-1255
• 26 Carter JJ, Koutsky LA, Hughes JP. , et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 2000; 181 (06) 1911-1919
• 27 Edelstein ZR, Carter JJ, Garg R. , et al. Serum antibody response following genital alpha9 human papillomavirus infection in young men. J Infect Dis 2011; 204 (02) 209-216
• 28 Rodríguez AC, Schiffman M, Herrero R. , et al; Proyecto Epidemiológico Guanacaste Group. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst 2008; 100 (07) 513-517
• 29 FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007; 356 (19) 1915-1927
• 30 Lehtinen M, Paavonen J, Wheeler CM. , et al; HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012; 13 (01) 89-99
• 31 Wentzensen N, Rodriguez AC, Viscidi R. , et al. A competitive serological assay shows naturally acquired immunity to human papillomavirus infections in the Guanacaste Natural History Study. J Infect Dis 2011; 204 (01) 94-102
• 32 Nyitray AG, Carvalho da Silva RJ, Baggio ML. , et al. Six-month incidence, persistence, and factors associated with persistence of anal human papillomavirus in men: the HPV in men study. J Infect Dis 2011; 204 (11) 1711-1722
• 33 Scholefield JH, Castle MT, Watson NFS. Malignant transformation of high-grade anal intraepithelial neoplasia. Br J Surg 2005; 92 (09) 1133-1136
• 34 Machalek DA, Poynten M, Jin F. , et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 2012; 13 (05) 487-500
• 35 Palefsky JM, Giuliano AR, Goldstone S. , et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365 (17) 1576-1585
• 36 Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD. ; Standards Practice Task Force of the American Society of Colon and Rectal Surgeons. Practice parameters for anal squamous neoplasms. Dis Colon Rectum 2012; 55 (07) 735-749
• 37 Nigro ND, Vaitkevicius VK, Buroker T, Bradley GT, Considine B. Combined therapy for cancer of the anal canal. Dis Colon Rectum 1981; 24 (02) 73-75
• 38 Doci R, Zucali R, La Monica G. , et al. Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients. J Clin Oncol 1996; 14 (12) 3121-3125
• 39 Anal Cancer: Statistics. Available at: www.cancer.net/cancer-types/anal-cancer/statistics
• 40 Markowitz LE, Hariri S, Lin C. , et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. J Infect Dis 2013; 208 (03) 385-393
• 41 Flagg EW, Schwartz R, Weinstock H. Prevalence of anogenital warts among participants in private health plans in the United States, 2003-2010: potential impact of human papillomavirus vaccination. Am J Public Health 2013; 103 (08) 1428-1435
• 42 Centers for Disease Control and Prevention (CDC). Recommendations on the use of quadrivalent human papillomavirus vaccine in males—Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep 2011; 60 (50) 1705-1708
• 43 Markowitz LE, Dunne EF, Saraiya M. , et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63 (RR-05): 1-30
• 44 Petrosky E, Bocchini Jr JA, Hariri S. , et al; Centers for Disease Control and Prevention (CDC). Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015; 64 (11) 300-304
• 45 www.cdc.gov/media/releases/2016/p1020-hpv-shots.html
• 46 Alexander M, Salgaller ML, Celis E. , et al. Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of cervical cancer patients by in vitro stimulation with a synthetic human papillomavirus type 16 E7 epitope. Am J Obstet Gynecol 1996; 175 (06) 1586-1593
• 47 Resnick MB, Finkelstein Y, Weissler A, Levy J, Yakirevich E. Assessment and diagnostic utility of the cytotoxic T-lymphocyte phenotype using the specific markers granzyme-B and TIA-1 in esophageal mucosal biopsies. Hum Pathol 1999; 30 (04) 397-402
• 48 Evans EM, Man S, Evans AS, Borysiewicz LK. Infiltration of cervical cancer tissue with human papillomavirus-specific cytotoxic T-lymphocytes. Cancer Res 1997; 57 (14) 2943-2950
• 49 Nakagawa M, Stites DP, Patel S. , et al. Persistence of human papillomavirus type 16 infection is associated with lack of cytotoxic T lymphocyte response to the E6 antigens. J Infect Dis 2000; 182 (02) 595-598
• 50 McFadden G, Kane K. How DNA viruses perturb functional MHC expression to alter immune recognition. Adv Cancer Res 1994; 63: 117-209
• 51 Bontkes HJ, de Gruijl TD, Walboomers JM. , et al. Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions. Br J Cancer 1997; 76 (10) 1353-1360
• 52 Loddenkemper C, Hoffmann C, Stanke J. , et al. Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer. Cancer Sci 2009; 100 (06) 1112-1117
• 53 Morris VK, Ciombor KK, Salem ME. , et al. NCI9673: A multi-institutional eETCTN phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal (SCCA). J Clin Oncol 2016; 34 (15, Suppl): 3503
• 54 García-Hernández E, González-Sánchez JL, Andrade-Manzano A. , et al. Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine. Cancer Gene Ther 2006; 13 (06) 592-597
• 55 Rosales R, López-Contreras M, Rosales C. , et al. Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine. Hum Gene Ther 2014; 25 (12) 1035-1049
• 56 Vreeland TJ, Clifton GT, Herbert GS. , et al. Gaining ground on a cure through synergy: combining checkpoint inhibitors with cancer vaccines. Expert Rev Clin Immunol 2016; 12 (12) 1347-1357
• 57 Berry J, Vreeland T, Trappey A. , et al. Cancer vaccines in colon and rectal cancer over the last decade: lessons learned and future directions. Expert Rev Clin Immunol 2017; 13 (03) 235-245