A 2020 update of anal cancer: the increasing problem in women and expanding treatment landscape

References

• The global cancer observatory. Anus fact sheet. (Ed.^(Eds) (Globocan, The World Health Organisation, 2019)
   Google Scholar
• Herfs M, Roncarati P, Koopmansch B, et al. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine. Br J Cancer. 2018;118(10):1302–1312.
   PubMed Web of Science ®Google Scholar
• Roy AC, Wattchow D, Astill D, et al. Uncommon anal neoplasms. Surg Oncol Clin N Am. 2017;26(1):143–161.
   PubMed Web of Science ®Google Scholar
• Colón-López V, Shiels MS, Machin M, et al. Anal cancer risk among people with HIV infection in the United States. J Clin Oncol. 2018;36(1):68–75.
   PubMed Web of Science ®Google Scholar
• Sundel MH, Voltaggio L, Leeds IL, et al. Anatomy and histology of the anus. In: Meyer J, Kachnic L, editors. Anal Cancer: A Comprehensive Guide. Cham: Springer International Publishing; 2019. p. 1–9.
   Google Scholar
• Herfs M, Longuespée R, Quick CM, et al. Proteomic signatures reveal a dualistic and clinically relevant classification of anal canal carcinoma. J Pathol. 2017;241(4):522–533.
   PubMed Web of Science ®Google Scholar
• Herfs M, Yamamoto Y, Laury A, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Nat Acad Sci. 2012;109(26):10516.
   PubMed Web of Science ®Google Scholar
• Herfs M, Soong TR, Delvenne P, et al. Deciphering the multifactorial susceptibility of mucosal junction cells to HPV infection and related carcinogenesis. Viruses. 2017;9:4.
   Web of Science ®Google Scholar
• Darragh TM, Colgan TJ, Thomas Cox J, et al. 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. 2013;32(1):76–115.
   PubMed Web of Science ®Google Scholar
• Scholefield JH, Castle MT, Watson NFS. Malignant transformation of high-grade anal intraepithelial neoplasia. BJS (British Journal of Surgery). 2005;92(9):1133–1136.
   PubMed Web of Science ®Google Scholar
• Tong WW, Jin F, McHugh LC, et al. Progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions in HIV-infected and uninfected men. Aids. 2013;27(14):2233–2243.
   PubMed Web of Science ®Google Scholar
• Watson AJM, Smith BB, Whitehead MR, et al. Malignant progression of anal intra-epithelial neoplasia. ANZ J Surg. 2006;76(8):715–717.
   PubMed Web of Science ®Google Scholar
• Lee GC, Kunitake H, Milch H, et al. What is the risk of anal carcinoma in patients with anal intraepithelial neoplasia III? Dis Colon Rectum. 2018;61(12):1350–1356.
   PubMed Web of Science ®Google Scholar
• Maugin F, Lesage AC, Hoyeau N, et al. Early detection of anal high-grade squamous intraepithelial lesion: do we have an impact on progression to invasive anal carcinoma? J Low Genit Tract Dis. 2020;24(1):82–86.
   PubMed Web of Science ®Google Scholar
• Schiffman M, Wentzensen N. Human papillomavirus infection and the multistage carcinogenesis of cervical cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(4):553–560.
   PubMed Web of Science ®Google Scholar
• Kang YJ, Smith M, Canfell K. Anal cancer in high-income countries: increasing burden of disease. PLoS One. 2018;13(10):e0205105.
   PubMed Web of Science ®Google Scholar
• Islami F, Ferlay J, Lortet-Tieulent J, et al. International trends in anal cancer incidence rates. Int J Epidemiol. 2017;46(3):924–938.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2018;68(1):7–30.
   PubMed Web of Science ®Google Scholar
• Deshmukh AA, Suk R, Shiels MS, et al. Recent trends in squamous cell carcinoma of the anus incidence and mortality in the United States, 2001–2015. JNCI. 2019. DOI: 10.1093/jnci/djz219
   PubMedGoogle Scholar
• Hawley-Nelson P, Vousden KH, Hubbert NL, et al. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. Embo J. 1989;8(12):3905–3910.
   PubMed Web of Science ®Google Scholar
• Münger K, Phelps WC, Bubb V, et al. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol. 1989;63(10):4417–4421.
   PubMed Web of Science ®Google Scholar
• Münger K, Baldwin A, Edwards KM, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78(21):11451–11460.
   PubMed Web of Science ®Google Scholar
• Ghittoni R, Accardi R, Hasan U, et al. The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes. 2010;40(1):1–13.
   PubMed Web of Science ®Google Scholar
• Venuti A, Paolini F, Nasir L, et al. Papillomavirus E5: the smallest oncoprotein with many functions. Mol Cancer. 2011;10:140.
   PubMed Web of Science ®Google Scholar
• Morris V, Rao X, Pickering C, et al. Comprehensive genomic profiling of metastatic squamous cell carcinoma of the anal canal. Mol Cancer Res. 2017;15(11):1542–1550.
   PubMed Web of Science ®Google Scholar
• Werness B, Levine A, Howley P. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248(4951):76–79.
   PubMed Web of Science ®Google Scholar
• Lin C, Franceschi S, Clifford GM. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis. Lancet Infect Dis. 2018;18(2):198–206.
   PubMed Web of Science ®Google Scholar
• McQuillan GK-MD, Markowitz LE, Unger ER, et al. Prevalence of HPV in adults aged 18–69: united States, 2011–2014. Hyattsville, MD: National Center for Health Statistics.; 2017.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lin C, Slama J, Gonzalez P, et al. Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis. Lancet Infect Dis. 2019;19(8):880–891.
   PubMed Web of Science ®Google Scholar
• Shvetsov YB, Hernandez BY, McDuffie K, et al. Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study. Clin Infect Dis. 2009;48(5):536–546.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Wei F, Su Y, Yao X, et al. Sex differences in the incidence and clearance of anal human papillomavirus infection among heterosexual men and women in Liuzhou, China: an observational cohort study. Int J Cancer. 2019;145(3):807–816.
   PubMed Web of Science ®Google Scholar
• Beachler DC, D’Souza G, Sugar EA, et al. Natural history of anal vs oral HPV infection in HIV-infected men and women. J Infect Dis. 2013;208(2):330–339.
   PubMed Web of Science ®Google Scholar
• Barroso LF 2nd. The role of Human Papilloma Virus (HPV) vaccination in the prevention of anal cancer in individuals with Human Immunodeficiency Virus-1 (HIV-1) infection. Ther Adv Vaccines. 2013;1(2):81–92.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Swedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis. 2012;54(7):891–898.
   PubMed Web of Science ®Google Scholar
• Dion GR, Teng S, Boyd LR, et al. Adjuvant human papillomavirus vaccination for secondary prevention: a systematic review. JAMA Otolaryngol Head Neck Surg. 2017;143(6):614–622.
   PubMed Web of Science ®Google Scholar
• Joura EA, Garland SM, Paavonen J, et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. 2012;344:e1401–e1401.
   PubMedGoogle Scholar
• Roberts J, Lee M, Stockbridge L, et al. Clinical review of biologics license application supplement STN# 125126/773—mid-adult women indication for GARDASIL. FDA. 2011; Available at: http://www. fda. gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094042. htm
   Google Scholar
• Ghelardi A, Parazzini F, Martella F, et al. SPERANZA project: HPV vaccination after treatment for CIN2. Gynecol Oncol. 2018;151(2):229–234.
   PubMed Web of Science ®Google Scholar
• Swedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clinl Infect Dis. 2012;54(7):891–898.
   PubMed Web of Science ®Google Scholar
• Gilbert DC, Wakeham K, Langley RE, et al. Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis. Br J Cancer. 2019;120(2):256–268.
   PubMed Web of Science ®Google Scholar
• Jemal A, Simard EP, Dorell C, et al. 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. 2013;105(3):175–201.
   PubMed Web of Science ®Google Scholar
• Machalek DA, Garland SM, Brotherton JML, et al. Very low prevalence of vaccine human papillomavirus types among 18- to 35-year old australian women 9 years following implementation of vaccination. J Infect Dis. 2018;217(10):1590–1600.
   PubMed Web of Science ®Google Scholar
• Patel C, Brotherton JM, Pillsbury A, et al. The impact of 10 years of human papillomavirus (HPV) vaccination in Australia: what additional disease burden will a nonavalent vaccine prevent? Euro Surveill. 2018;23(41):1700737.
   Google Scholar
• Shiels MS, Pfeiffer RM, Chaturvedi AK, et al. Impact of the HIV epidemic on the incidence rates of anal cancer in the United States. J Natl Cancer Inst. 2012;104(20):1591–1598.
   PubMedGoogle Scholar
• Frisch M, Glimelius B, van den Brule AJ, et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337(19):1350–1358.
   PubMed Web of Science ®Google Scholar
• Chaturvedi AK, Engels EA, Gilbert ES, et al. Second cancers among 104760 survivors of cervical cancer: evaluation of long-term risk. JNCI. 2007;99(21):1634–1643.
   PubMedGoogle Scholar
• Teng C-J, Huon L-K, Hu Y-W, et al. Secondary primary malignancy risk in patients with cervical cancer in Taiwan: a nationwide population-based study. Medicine (Baltimore). 2015;94(43):e1803–e1803.
   PubMed Web of Science ®Google Scholar
• Ebisch RMF, Rutten DWE, IntHout J, et al. Long-lasting increased risk of human papillomavirus–related carcinomas and premalignancies after cervical intraepithelial neoplasia grade 3: a population-based cohort study. J clin oncol. 2017;35(22):2542–2550.
   PubMed Web of Science ®Google Scholar
• Coffey K, Beral V, Green J, et al., on behalf of the Million Women Study C. Lifestyle and reproductive risk factors associated with anal cancer in women aged over 50 years. Br J Cancer. 2015;112(9):1568–1574.
   PubMed Web of Science ®Google Scholar
• Frisch M, Glimelius B, Wohlfahrt J, et al. Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism? J Natl Cancer Inst. 1999;91(8):708–715.
   PubMedGoogle Scholar
• Nordenvall C, Nilsson PJ, Ye W, et al. Smoking, snus use and risk of right- and left-sided colon, rectal and anal cancer: A 37-year follow-up study. Int J Cancer. 2011;128(1):157–165.
   PubMed Web of Science ®Google Scholar
• Ramamoorthy S, Luo L, Luo E, et al. Tobacco smoking and risk of recurrence for squamous cell cancer of the anus. Cancer Detect Prev. 2008;32(2):116–120.
   PubMedGoogle Scholar
• Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370(9581):59–67.
   PubMed Web of Science ®Google Scholar
• Mysliwiec PA, Arthur Schatzkin KAC, New malignancies following cancer of the colon, rectum, and anus in: new malignancies among cancer survivors: SEER cancer registries, 1973-2000. Curtis, R, Freedman, D, Ron, E et al. (Eds.) (National Cancer Institute, Bethesda, MD, 2006) 111–144.
   Google Scholar
• Leo PJ, Madeleine MM, Wang S, et al. Defining the genetic susceptibility to cervical neoplasia—A genome-wide association study. PLoS Genet. 2017;13(8):e1006866.
   PubMed Web of Science ®Google Scholar
• Okuyama NCM, Cezar-dos-Santos F, Pereira ÉR, et al. Genetic variant in CXCL12 gene raises susceptibility to HPV infection and squamous intraepithelial lesions development: a case-control study. J Biomed Sci. 2018;25(1):69.
   PubMedGoogle Scholar
• Read T, Vodstrcil L, Grulich A, et al. Acceptability of digital anal cancer screening examinations in HIV-positive homosexual men. HIV Med. 2013;14(8):491–496.
   PubMed Web of Science ®Google Scholar
• Machalek DA, Grulich AE, Hillman RJ, et al. The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study. BMC Public Health. 2013;13:946.
   PubMed Web of Science ®Google Scholar
• Gonçalves JCN, Macedo ACL, Madeira K, et al. Accuracy of anal cytology for diagnostic of precursor lesions of anal cancer: systematic review and meta-analysis. Dis Colon Rectum. 2019;62(1):112–120.
   PubMed Web of Science ®Google Scholar
• Ramos-Cartagena JM, Perez CM, Guiot HM, et al. Assessment of anal cancer screening tools in detecting high-grade anal squamous intraepithelial lesions in women. J Low Genit Tract Dis. 2020;24(1):75–81.
   PubMed Web of Science ®Google Scholar
• Clarke MA, Cheung LC, Lorey T, et al. 5-year prospective evaluation of cytology, human papillomavirus testing, and biomarkers for detection of anal precancer in human immunodeficiency virus-positive men who have sex with men. Clin Infect Dis. 2019;69(4):631–638.
   PubMed Web of Science ®Google Scholar
• Albuquerque A, Sheaff M, Stirrup O, et al. Performance of anal cytology compared with high-resolution anoscopy and histology in women with lower anogenital tract neoplasia. Clinl Infect Dis. 2018;67(8):1262–1268.
   PubMed Web of Science ®Google Scholar
• Moscicki A-B, Hills NK, Shiboski S, et al. Risk factors for abnormal anal cytology in young heterosexual women. Cancer Epidemiol Biomarkers Prev. 1999;8(2):173–178.
   PubMed Web of Science ®Google Scholar
• Palefsky JM. Practising high-resolution anoscopy. Sex Health. 2012;9(6):580–586.
   PubMed Web of Science ®Google Scholar
• Jay N. High-resolution anoscopy: procedure and findings. Semin Colon and Rectal Surg. 2017;28(2):75–80.
   Web of Science ®Google Scholar
• Hillman RJ, Gunathilake MPW, Jin F, et al. Ability to detect high-grade squamous anal intraepithelial lesions at high resolution anoscopy improves over time. Sexual Health (Online). 2016;13(2):177–181.
   PubMed Web of Science ®Google Scholar
• AIDS malignancy consortium. Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions (ANCHOR). (Ed.^(Eds) (2014)
   Google Scholar
• Goldstone SE, Lensing SY, Stier EA, et al. A randomized clinical trial of infrared coagulation ablation versus active monitoring of intra-anal high-grade dysplasia in adults with human immunodeficiency virus infection: an AIDS malignancy consortium trial. Clinl Infect Dis. 2018;68(7):1204–1212.
   Web of Science ®Google Scholar
• Megill C, Wilkin T. Topical therapies for the treatment of anal high-grade squamous intraepithelial lesions. Semin Colon Rectal Surg. 2017;28(2):86–90.
   PubMed Web of Science ®Google Scholar
• Garbuglia AR, Lapa D, Sias C, et al. The use of both therapeutic and prophylactic vaccines in the therapy of papillomavirus disease. Front Immunol. 2020;11(188).
   PubMedGoogle Scholar
• Leppard S. Anal cancer is on the rise; it’s a shame …. Aust Fam Physician. 2016;45:252–253.
   PubMedGoogle Scholar
• Longabaugh M. Patient perspective and personal journey of treating a “Rare Cancer”. Surg Oncol Clin N Am. 2017;26(1):1–7.
   PubMed Web of Science ®Google Scholar
• Chang EM, Shaverdian N, Lee P, et al. The patient’s perspective on chemoradiation for anal cancer: evaluation of expectations and stigma. Int J Radiat Oncol Biol Phys. 2019;105(1):E592–E593.
   Web of Science ®Google Scholar
• Welton ML, Steele SR, Goodman KA et al. Anus (ed. Amin, M) (AJCC, Chicago, 2017).
   Google Scholar
• Goffredo P, Garancini M, Robinson TJ, et al. A National-Level Validation of the New American Joint Committee on cancer 8th edition subclassification of stage IIA and B anal squamous cell cancer. Ann Surg Oncol. 2018;25(6):1654–1660.
   PubMed Web of Science ®Google Scholar
• Granata V, Fusco R, Reginelli A, et al. Radiological assessment of anal cancer: an overview and update. Infect Agent Cancer. 2016;11(1):52.
   PubMedGoogle Scholar
• Jones M, Hruby G, Solomon M, et al. The role of FDG-PET in the initial staging and response assessment of anal cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2015;22(11):3574–3581.
   PubMed Web of Science ®Google Scholar
• Gauthé M, Richard-Molard M, Fayard J, et al. Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer. Eur J Nucl Med Mol Imaging. 2017;44(1):63–70.
   PubMed Web of Science ®Google Scholar
• Mohammadkhani Shali S, Schmitt V, Behrendt FF, et al. Metabolic tumour volume of anal carcinoma on (18)FDG PET/CT before combined radiochemotherapy is the only independent determinant of recurrence free survival. Eur J Radiol. 2016;85(8):1390–1394.
   PubMed Web of Science ®Google Scholar
• Nigro ND, Vaitkevicius VK, Considine BJ. Combined therapy for cancer of the anal canal: A preliminary report. Dis Colon Rectum. 1974;17(3):354–356.
   PubMed Web of Science ®Google Scholar
• Flam M, John M, Pajak TF, et al. 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. 1996;14(9):2527–2539.
   PubMed Web of Science ®Google Scholar
• Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(16):1914–1921.
   PubMed Web of Science ®Google Scholar
• Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997;15(5):2040–2049.
   PubMed Web of Science ®Google Scholar
• Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR anal cancer trial working party. UK co-ordinating committee on cancer research. Lancet. 1996;348(9034):1049–1054.
   PubMed Web of Science ®Google Scholar
• Gunderson LL, Winter KA, Ajani JA, et al. 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. 2012;30(35):4344–4351.
   PubMed Web of Science ®Google Scholar
• Goodman KA, Julie D, Cercek A, et al. Capecitabine with mitomycin reduces acute hematologic toxicity and treatment delays in patients undergoing definitive chemoradiation using intensity modulated radiation therapy for anal cancer. Int J Radiat Oncol Biol Phys. 2017;98(5):1087–1095.
   PubMed Web of Science ®Google Scholar
• Oliveira SCR, Moniz CMV, Riechelmann R, et al. 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. 2016;47(1):75–81.
   PubMedGoogle Scholar
• Glynne-Jones R, Meadows H, Wan S, et al. EXTRA–a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys. 2008;72(1):119–126.
   PubMed Web of Science ®Google Scholar
• Thind G, Johal B, Follwell M, et al. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Radiat Oncol. 2014;9:124.
   PubMed Web of Science ®Google Scholar
• Meulendijks D, Dewit L, Tomasoa NB, et al. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J Cancer. 2014;111(9):1726–1733.
   PubMed Web of Science ®Google Scholar
• James RD, Glynne-Jones R, Meadows HM, et al. 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. 2013;14(6):516–524.
   PubMed Web of Science ®Google Scholar
• Peiffert D, Tournier-Rangeard L, Gérard J-P, et al. 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. 2012;30(16):1941–1948.
   PubMed Web of Science ®Google Scholar
• Nigro ND, Seydel HG, Considine B, et al. Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 1981;7(9):1279–1280.
   Web of Science ®Google Scholar
• Weber DC, Kurtz JM, Allal AS. The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys. 2001;50(3):675–680.
   PubMed Web of Science ®Google Scholar
• Graf R, Wust P, Hildebrandt B, et al. Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology. 2003;65(1):14–22.
   PubMed Web of Science ®Google Scholar
• Ben-Josef E, Moughan J, Ajani JA, et al. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of radiation therapy oncology group trials 87-04 and 98-11. J Clin Oncol. 2010;28(34):5061–5066.
   PubMed Web of Science ®Google Scholar
• Raphael MJ, Ko G, Booth CM, et al. Factors associated with chemoradiation therapy interruption and noncompletion among patients with squamous cell anal carcinoma. JAMA Oncol. 2020 Apr 23.
   PubMed Web of Science ®Google Scholar
• Rattan R, Kapoor R, Bahl A, et al. Comparison of bone marrow sparing intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in carcinoma of anal canal: a prospective study. Ann Transl Med. 2016;4(4):70.
   PubMed Web of Science ®Google Scholar
• Mitra D, Hong TS, Horick N, et al. Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529. Adv Radiat Oncol. 2017;2(2):110–117.
   PubMedGoogle Scholar
• Kachnic LA, Winter K, Myerson RJ, et al. 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. 2013;86(1):27–33.
   PubMed Web of Science ®Google Scholar
• Knowles G, Haigh R, McLean C, et al. Late effects and quality of life after chemo-radiation for the treatment of anal cancer. Eur J Oncol Nurs. 2015;19(5):479–485.
   PubMed Web of Science ®Google Scholar
• Sterner A, Derwinger K, Staff C, et al. Quality of life in patients treated for anal carcinoma-a systematic literature review. Int J Colorectal Dis. 2019;34(9):1517–1528.
   PubMed Web of Science ®Google Scholar
• Joseph K, Vos LJ, Warkentin H, et al. Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer. Radiother Oncol. 2016;120(2):228–233.
   PubMed Web of Science ®Google Scholar
• Sunesen KG, Norgaard M, Lundby L, et al. Long-term anorectal, urinary and sexual dysfunction causing distress after radiotherapy for anal cancer: a Danish multicentre cross-sectional questionnaire study. Colorectal Dis. 2015;17(11):O230–239.
   PubMed Web of Science ®Google Scholar
• Jensen PT, Froeding LP. Pelvic radiotherapy and sexual function in women. Transl Androl Urol. 2015;4(2):186–205.
   PubMed Web of Science ®Google Scholar
• Mirabeau-Beale K, Hong TS, Niemierko A, et al. Clinical and treatment factors associated with vaginal stenosis after definitive chemoradiation for anal canal cancer. Pract Radiat Oncol. 2015;5(3):e113–118.
   PubMed Web of Science ®Google Scholar
• Savoie MB, Laffan A, Brickman C, et al. A multi-disciplinary model of survivorship care following definitive chemoradiation for anal cancer. BMC Cancer. 2019;19(1):906.
   PubMed Web of Science ®Google Scholar
• DuHamel K, Schuler T, Nelson C, et al. The sexual health of female rectal and anal cancer survivors: results of a pilot randomized psycho-educational intervention trial. J Cancer Surviv. 2016;10(3):553–563.
   PubMed Web of Science ®Google Scholar
• Glynne-Jones R, Sebag-Montefiore D, Meadows HM, et al. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a posthoc analysis of randomised controlled phase 3 trial. Lancet Oncol. 2017;18(3):347–356.
   PubMed Web of Science ®Google Scholar
• Koh DM, Dzik-Jurasz A, O’Neill B, et al. Pelvic phased-array MR imaging of anal carcinoma before and after chemoradiation. Br J Radiol. 2008;81(962):91–98.
   PubMed Web of Science ®Google Scholar
• Durot C, Dohan A, Boudiaf M, et al. Cancer of the anal canal: diagnosis, staging and follow-up with MRI. Korean J Radiol. 2017;18(6):946–956.
   PubMed Web of Science ®Google Scholar
• Kochhar R, Renehan AG, Mullan D, et al. The assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer. Eur Radiol. 2017;27(2):607–617.
   PubMed Web of Science ®Google Scholar
• Jones MP, Hruby G, Metser U, et al. FDG-PET parameters predict for recurrence in anal cancer – results from a prospective, multicentre clinical trial. Radiat Oncol. 2019;14(1):140.
   PubMed Web of Science ®Google Scholar
• Hocquelet A, Auriac T, Perier C, et al. Pre-treatment magnetic resonance-based texture features as potential imaging biomarkers for predicting event free survival in anal cancer treated by chemoradiotherapy. Eur Radiol. 2018;28(7):2801–2811.
   PubMed Web of Science ®Google Scholar
• Brown PJ, Zhong J, Frood R, et al. Prediction of outcome in anal squamous cell carcinoma using radiomic feature analysis of pre-treatment FDG PET-CT. Eur J Nucl Med Mol Imaging. 2019;46(13):2790–2799.
   PubMed Web of Science ®Google Scholar
• Mullen JT, Rodriguez-Bigas MA, Chang GJ, et al. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol. 2007;14(2):478–483.
   PubMed Web of Science ®Google Scholar
• Hagemans J, Blinde S, Nuyttens J, et al. Salvage abdominoperineal resection for squamous cell anal cancer: a 30-year single-institution experience. Ann Surg Oncol. 2018;25:1970–1979.
   Google Scholar
• Eeson G, Foo M, Harrow S, et al. Outcomes of salvage surgery for epidermoid carcinoma of the anus following failed combined modality treatment. Am J Surg. 2011;201(5):628–633.
   PubMed Web of Science ®Google Scholar
• Lefèvre JH, Corte H, Tiret E, et al. Abdominoperineal resection for squamous cell anal carcinoma: survival and risk factors for recurrence. Ann Surg Oncol. 2012;19(13):4186–4192.
   PubMed Web of Science ®Google Scholar
• Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, et al. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol. 2014;32(17):1812–1817.
   PubMed Web of Science ®Google Scholar
• Sun G, Dong X, Tang X, et al. The prognostic value of HPV combined p16 status in patients with anal squamous cell carcinoma: a meta-analysis. Oncotarget. 2017;9(8):8081–8088.
   PubMedGoogle Scholar
• Parwaiz I, MacCabe TA, Thomas MG, et al. A systematic review and meta-analysis of prognostic biomarkers in anal squamous cell carcinoma treated with primary chemoradiotherapy. Clin Oncol (R Coll Radiol). 2019;31(12):e1–e13.
   PubMed Web of Science ®Google Scholar
• Meulendijks D, Tomasoa NB, Dewit L, et al. HPV-negative squamous cell carcinoma of the anal canal is unresponsive to standard treatment and frequently carries disruptive mutations in TP53. Br J Cancer. 2015;112(8):1358–1366.
   PubMed Web of Science ®Google Scholar
• Gilbert DC, Williams A, Allan K, et al. p16INK4A, p53, EGFR expression and KRAS mutation status in squamous cell cancers of the anus: correlation with outcomes following chemo-radiotherapy. Radiother Oncol. 2013;109(1):146–151.
   PubMed Web of Science ®Google Scholar
• Bernard-Tessier A, Jeannot E, Guenat D, et al. Clinical validity of HPV circulating tumor DNA in advanced anal carcinoma: an ancillary study to the epitopes-HPV02 trial. Clin Cancer Res. 2019;25(7):2109–2115.
   PubMed Web of Science ®Google Scholar
• Toh E, Wilson J, Sebag-Montefiore D, et al. Neutrophil:lymphocyte ratio as a simple and novel biomarker for prediction of locoregional recurrence after chemoradiotherapy for squamous cell carcinoma of the anus. Colorectal Dis. 2014;16(3):O90–O97.
   PubMed Web of Science ®Google Scholar
• Bulla R, Humes D, Scholefield J, et al. PTU-205 The significance of elevated neutrophil: lymphocyte ratios in patients receiving chemoradiotherapy treatment for squamous cell carcinoma of the anus. Gut. 2015;64(Suppl 1):A153–A153.
   Google Scholar
• Casadei-Gardini A, Montagnani F, Casadei C, et al. Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: anal cancer response classifier). Cancer Manag Res. 2019;11:3631–3642.
   PubMed Web of Science ®Google Scholar
• Balermpas P, Martin D, Wieland U, et al. Human papilloma virus load and PD-1/PD-L1, CD8(+) and FOXP3 in anal cancer patients treated with chemoradiotherapy: rationale for immunotherapy. Oncoimmunology. 2017;6(3):e1288331–e1288331.
   PubMed Web of Science ®Google Scholar
• Gilbert DC, Serup-Hansen E, Linnemann D, et al. Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer. Br J Cancer. 2016;114(2):134–137.
   PubMed Web of Science ®Google Scholar
• Faivre C, Rougier P, Ducreux M, et al. 5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer. Bull Cancer. 1999;86(10):861–865.
   PubMed Web of Science ®Google Scholar
• Tanum G. Treatment of relapsing anal carcinoma. Acta Oncol. 1993;32(1):33–35.
   PubMed Web of Science ®Google Scholar
• Jaiyesimi IA, Pazdur R. Cisplatin and 5-fluorouracil as salvage therapy for recurrent metastatic squamous cell carcinoma of the anal canal. Am J Clin Oncol. 1993;16(6):536–540.
   PubMed Web of Science ®Google Scholar
• Rao S, Sclafani F, Eng C, et al. LBA21InterAACT: A multicentre open label randomised phase II advanced anal cancer trial of cisplatin (CDDP) plus 5-fluorouracil (5-FU) vs carboplatin (C) plus weekly paclitaxel (P) in patients (pts) with inoperable locally recurrent (ILR) or metastatic treatment naïve disease - An International Rare Cancers Initiative (IRCI) trial. Ann Oncol. 2018; 29(suppl_8):abstr LBA21.
   Google Scholar
• Mondaca S, Chatila WK, Bates D, et al. FOLFCIS treatment and genomic correlates of response in advanced anal squamous cell cancer. Clin Colorectal Cancer. 2019;18(1):e39–e52.
   PubMed Web of Science ®Google Scholar
• Matsunaga M, Miwa K, Oka Y, et al. Successful treatment of metastatic anal canal adenocarcinoma with mFOLFOX6 + Bevacizumab. Case Rep Oncol. 2016;9(1):249–254.
   PubMed Web of Science ®Google Scholar
• Kim S, François E, André T, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018;19(8):1094–1106.
   PubMed Web of Science ®Google Scholar
• Symer MM, Yeo HL Recent advances in the management of anal cancer. F1000Res, 7, F1000 Faculty Rev-1572 (2018).
   Google Scholar
• Welters MJP, de Jong A, van den Eeden SJF, et al. Frequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter. Cancer Res. 2003;63(3):636–641.
   PubMed Web of Science ®Google Scholar
• Smola S. Immunopathogenesis of HPV-associated cancers and prospects for immunotherapy. Viruses. 2017;9(9):254.
   Web of Science ®Google Scholar
• Puronen CE, Ford ES, Uldrick TS. Immunotherapy in people with HIV and cancer. Front Immunol. 2019;10(2060). DOI: 10.3389/fimmu.2019.02060
   PubMedGoogle Scholar
• Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28(5):1036–1041.
   PubMed Web of Science ®Google Scholar
• Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): results from the multicohort, phase II KEYNOTE-158 study. J clin oncol. 2020;38(4_suppl):1.
   PubMed Web of Science ®Google Scholar
• Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(4):446–453.
   PubMed Web of Science ®Google Scholar
• Sebag-Montefiore D, Adams R, Bell S, et al. The development of an umbrella trial (PLATO) to address radiation therapy dose questions in the locoregional management of squamous cell carcinoma of the anus. Int J Radiat Oncol Biol Phys. 2016;96(2):E164–E165.
   Web of Science ®Google Scholar
• Hinrichs CS. Molecular pathways: breaking the epithelial cancer barrier for chimeric antigen receptor and T-cell receptor gene therapy. Clin Cancer Res. 2016;22(7):1559–1564.
   PubMed Web of Science ®Google Scholar
• Hinrichs CS, Doran SL, Stevanovic S, et al. A phase I/II clinical trial of E6 T-cell receptor gene therapy for human papillomavirus (HPV)-associated epithelial cancers. J clin oncol. 2017;35(15_suppl):3009.
   Google Scholar
• Doran SL, Stevanović S, Adhikary S, et al. T-cell receptor gene therapy for human papillomavirus–associated epithelial cancers: a first-in-human, phase I/II study. J clin oncol. 2019;37(30):2759–2768.
   PubMed Web of Science ®Google Scholar
• Stevanovic S, Helman SR, Wunderlich JR et al. A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers. Clinical Cancer Research, clincanres.2722.2018 (2018).
   Google Scholar
• Ma Y, Yang A, Peng S, et al. Characterization of HPV18 E6-specific T cell responses and establishment of HPV18 E6-expressing tumor model. Vaccine. 2017;35(31):3850–3858.
   PubMed Web of Science ®Google Scholar
• Bartkowiak T, Singh S, Yang G, et al. Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine. Proc Natl Acad Sci U S A. 2015;112(38):E5290–E5299.
   PubMed Web of Science ®Google Scholar
• The national library of medicine. ClinicalTrials.gov. (Ed.^(Eds) (United States of America, 2020)
   Google Scholar