Current Oncology Reports

, Volume 15, Issue 4, pp 287–295

The Adolescent and Young Adult With Cancer: State of the Art—Epithelial Cancer

  • Carlos G. Ferreira
  • Andréia Cristina de Melo
  • Angélica Nogueira-Rodrigues
Pediatric Oncology (S Epelman, Section Editor)


The adolescent and young adult (AYA) is defined as a patient of 15 to 39 years of age at initial cancer diagnosis, and this group has particular medical needs and age-related issues. Excluding violent deaths, cancer is the leading cause of death among the AYA population. Lymphomas, melanoma, testicular cancer, female genital tract malignancies, thyroid cancer, bone and soft tissue sarcomas, leukemias, central nervous system tumors, breast cancer, and nongonadal germ cell tumors account for 95 % of the cancers in this group. Among those, the epithelial cancer of AYA comprehends the minimum amount and its incidence rates tend to increase with age. This review presents information about epidemiology, biologic peculiarities, as well as standard treatment strategies for epithelial cancers in AYA.


Adolescent Young adult Epithelial cancer 


Papers of particular interest, published recently, have been highligted as: • Of importance •• Of major importance

  1. 1.
    Closing the gap: research and care imperatives for adolescents and young adults with cancer report of the Adolescent and Young Adult Oncology Progress Review Group. Accessed February 2013.
  2. 2.
    Bleyer A. Young adult oncology: the patients and their survival challenges. CA Cancer J Clin. 2007;57:242–55.PubMedCrossRefGoogle Scholar
  3. 3.
    Bleyer A, Viny A, Barr R. Cancer in 15- to 29-year-olds by primary site. Oncologist. 2006;11:590–601.PubMedCrossRefGoogle Scholar
  4. 4.
    Bleyer A, O’Leary M, Barr R, Ries L, eds: Cancer epidemiology in older adolescents and young adults 15 to 29 years of age, including SEER incidence and survival: 1975–2000. National Cancer Institute, NIH Pub. No. 06–5767. Bethesda, MD 2006.Google Scholar
  5. 5.
    Burke ME, Albritton K, Marina N. Challenges in the recruitment of adolescents and young adults to cancer clinical trials. Cancer. 2007;110:2385–93.PubMedCrossRefGoogle Scholar
  6. 6.
    Ferrari A, Montello M, Budd T, Bleyer A. The challenges of clinical trials for adolescents and young adults with cancer. Pediatr Blood Cancer. 2008;50:1101–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Bleyer A, Budd T, Montello M. Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials. Cancer. 2006;107:1645–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Cinar P, Zell JA, Taylor TH, et al. Pediatric and AYA invasive cutaneous melanoma: population-based study comparing adult melanoma cases. J Clin Oncol (ASCO Meeting Abstracts). 2008;26:9071.Google Scholar
  9. 9.
    Armstrong BK, Kricker A, English DR. Sun exposure and skin cancer. Australas J Dermatol. 1997;38(Suppl):S1–6.PubMedGoogle Scholar
  10. 10.
    Krengel S, Hauschild A, Schafer T. Melanoma risk in congenital melanocytic naevi: a systematic review. Br J Dermatol. 2006;155:1–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Youl P, Aitken J, Hayward N, et al. Melanoma in adolescents: a case–control study of risk factors in Queensland, Australia. Int J Cancer. 2002;98:92–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Pappo AS. Melanoma in children and adolescents. Eur J Cancer. 2003;39:2651–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Hannah KW, Hauschild A, Loraine DM, et al. Melanoma in adolescents and young adults (ages 15–39 years): United States, 1999–2006. J Am Acad Dermatol. 2011 November;65(5 Suppl 1):S38–49.Google Scholar
  14. 14.
    Chao MM, Schwartz JL, Wechsler DS, et al. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatr Blood Cancer. 2005;44:441–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Navid F, Furman WL, Fleming M, et al. The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer. 2005;103:780–7.PubMedCrossRefGoogle Scholar
  16. 16.
    • Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29:1239–46. Recent advances in melanoma predictive biomarkers.PubMedCrossRefGoogle Scholar
  17. 17.
    Daniotti M, Ferrari A, Frigerio S, et al. Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT. J Invest Dermatol. 2009;129:1759–68.PubMedCrossRefGoogle Scholar
  18. 18.
    • Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366:707–14. Recent advances in melanoma treatment.PubMedCrossRefGoogle Scholar
  19. 19.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  20. 20.
    Maggard MA, O’Connell JB, Lane KE, et al. Do young breast cancer patients have worse outcomes? J Surg Res. 2003;113:109–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Schairer C, Mink PJ, Carroll L, Devesa SS. Probabilities of death from breast cancer and other causes among female breast cancer patients. J Natl Cancer Inst. 2004;96:1311–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Xiong Q, Valero V, Kau V, et al. Female patients with breast carcinoma age 30 years and younger have a poor prog- nosis: the M.D. Anderson Cancer Center experience. Cancer. 2001;92:2523–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Ruddy KJ, Gelber S, Tamimi R, et al. Presentation of breast cancer in young women. J Clin Oncol. 2009;27:15s.CrossRefGoogle Scholar
  24. 24.
    Colleoni M, Rotmensz N, Robertson C, et al. Very young women (< 35 years) with operable breast cancer: features of disease at presentation. Ann Oncol. 2002;13(2):273–9.PubMedCrossRefGoogle Scholar
  25. 25.
    • Pronzato P, Mustacchi G, DeMatteis A, et al.: Biological Characteristics and Medical Treatment of Breast Cancer in Young Women - A Featured Population: Results from the NORA Study. Int J Breast Cancer 2011, article ID 534256, doi:10.4061/2011/534256. Comprehensive biologic data of breast cancer in young women.
  26. 26.
    Freedman RA. Adjuvant therapies for very young women with early stage breast cancer. Breast. 2001;20:146–9.CrossRefGoogle Scholar
  27. 27.
    •• Freedman RA, Virgo KS, Labadie J, et al. Receipt of locoregional therapy among young women with breast cancer. Breast Cancer Res Treat. 2012;135:893–906. Extensive data on locoregional treatment in AYA with breast cancer.PubMedCrossRefGoogle Scholar
  28. 28.
    Arvold ND, Taghian AG, Niemierko A, et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2011;29:3885–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Kroman N, Jensen MB, Wohlfahrt J, et al. Factors influencing the effect of age on prognosis in breast cancer: population based study. British Medical Journal. 2000;320:474–8.PubMedCrossRefGoogle Scholar
  30. 30.
    • Collaborative Group on Hormonal Factors in Breast Cancer: Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. The Lancet Oncology, Volume 13, Issue 11, Pages 1141–1151, November 2012. Meta-analysis of hormonal factors in breast cancer risk.Google Scholar
  31. 31.
    Davies C, Pan H, DPhil JG, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2012;381:805–16.CrossRefGoogle Scholar
  32. 32.
    Cuschieri KS, Cubie HA, Whitley MW, et al. Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population. J Clin Pathol. 2004;57:68–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Holowaty P, Miller AB, Rohan T, et al. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst. 1999;91:252–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Zur Hausen H. Papillomavirus and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Kawana K, Adachi K, Kojima S, Kozuma S, Fujii T. Therapeutic Human Papillomavirus (HPV) Vaccines: A Novel Approach. Open Virol J. 2012;6:264–9.PubMedCrossRefGoogle Scholar
  36. 36.
    •• Kardakis S: Fertility-preserving surgery in patients with early stage cervical carcinoma. ISRN Oncol. 2012, In press. Review of fertility-preserving surgery in cervical carcinoma.Google Scholar
  37. 37.
    Morris M, Mitchell MF, Silva EG, Copeland LJ, Gershenson DM. Cervical conization as definitive therapy for early invasive squamous carcinoma of the cervix. Gynecol Oncol. 1993;51:193–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Wright JD, Nathavith Arana R, Lewin SN, et al. Fertility- conserving surgery for young women with stage IA1 cervical cancer: safety and access. Obstet Gynecol. 2010;115:585–90.PubMedCrossRefGoogle Scholar
  39. 39.
    Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008;337:a1284.PubMedCrossRefGoogle Scholar
  40. 40.
    Rob L, Charvat M, Robova H, et al. Less radical fertility-sparing surgery than radical trachelectomy in early cervical cancer. Int J Gynecol Cancer. 2007;17:304–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Milliken DA, Shepherd JH. Fertility preserving surgery for carcinoma of the cervix. Curr Opin Oncol. 2008;20:575–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Jolley JA, Battista L, Wing DA. Management of pregnancy after radical trachelectomy: case reports and systematic review of the literature. Am J Perinatol. 2007;24:531–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Boss EA, van Golde RJ, Beerendonk CC, Massuger LF. Pregnancy after radical trachelectomy: a real option? Gynecol Oncol. 2005;99 Suppl 1:S152–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Whitney CW, Sause W, Bundy BN, et al. A randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages IIB- IVA carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecology Oncology Group and Southwest Oncology Group Study. J Clin Oncology. 1999;17:1339–48.Google Scholar
  45. 45.
    Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy versus pelvic and para-aortic radiation for high-risk cervical cancer: A randomized Radiation Therapy Oncologic Group clinical trial. N Engl J Med. 1999;340:1137–43.PubMedCrossRefGoogle Scholar
  46. 46.
    Peters III WA, Liu PY, Barret RJ, et al. Cisplatin and 5-fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive in high-risk early stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: Report of a phase III intergroup study. J Clin Oncol. 2000;18:1606–13.PubMedGoogle Scholar
  47. 47.
    Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin based chemoradiation improves progression free and overall survival in an advanced cervical cancer: Results of a randomized Gynecologic Oncology Group Study. N Engl J Med. 1999;340:1144–53.PubMedCrossRefGoogle Scholar
  48. 48.
    Keys HM, Bundy BM, Stehman FBV, et al. A comparison of weekly cisplatin during radiation therapy versus irradiation alone each followed by adjuvant hysterectomy in bulky stage IB cervical carcinoma: A randomized trial of the Gynecology Oncology Group. N Engl J Med. 1999;340:1154–61.PubMedCrossRefGoogle Scholar
  49. 49.
    National Cancer Institute: NCI Clinical Announcement, Bethesda, MD, United States. Department of Health and Human Services, Public Health Service, National Institutes of Health, February 1999.Google Scholar
  50. 50.
    Pearcey R, Brundage M, Drouin P, et al. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002;20:966–72.PubMedCrossRefGoogle Scholar
  51. 51.
    Tierney JF, Vale C, Symonds P. Concomitant and neoadjuvant chemotherapy for cervical cancer. Clin Oncol. 2008;20:401–16.CrossRefGoogle Scholar
  52. 52.
    Dursun P, Ayhan A, Yanik FB, Kuşçu E. Ovarian transposition for the preservation of ovarian function in young patients with cervical carcinoma. Eur J Gynaecol Oncol. 2009;30:13–5.PubMedGoogle Scholar
  53. 53.
    Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004;22:3113–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365:2041–54.PubMedCrossRefGoogle Scholar
  55. 55.
    • Buehrlen M, Zwaan CM, Granzen B, et al. Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer. 2012;118(19):4892–900. Combined therapy was well tolerated and resulted in a very good outcome, superior to the outcomes of published results from all other pediatric NPC study groups.PubMedCrossRefGoogle Scholar
  56. 56.
    Afqir S, Ismaili N, Alaoui K, et al. Nasopharyngeal carcinoma in adolescents: a retrospective review of 42 patients. Eur Arch Otorhinolaryngol. 2009;11:1767–73.CrossRefGoogle Scholar
  57. 57.
    Ayan I, Kaytan E, Ayan N. Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol. 2003;4:13–21.PubMedCrossRefGoogle Scholar
  58. 58.
    Song CH, Wu HG, Heo DS, et al. Treatment outcomes for radiotherapy alone are comparable with neoadjuvant chemotherapy followed by radiotherapy in early-stage nasopharyngeal carcinoma. Laryngoscope. 2008;118:663–70.PubMedCrossRefGoogle Scholar
  59. 59.
    Rodriguez-Galindo C, Wofford M, Castleberry RP, et al. Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma. Cancer. 2005;103:850–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Ozyar E, Selek U, Laskar S, et al. Treatment results of 165 pediatric patients with non-metastatic nasopharyngeal carcinoma: a Rare Cancer Network study. Radiother Oncol. 2006;81:39–46.PubMedCrossRefGoogle Scholar
  61. 61.
    Baujat B, Audry H, Bourhis J, et al. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006;64:47–56.PubMedCrossRefGoogle Scholar
  62. 62.
    Caponigro F, Longo F, Ionna F, Perri F. Treatment approaches to nasopharyngeal carcinoma: a review. Anticancer Drugs. 2010;21:471–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Hung W, Sarlis NJ. Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid. 2002;12:683–702.PubMedCrossRefGoogle Scholar
  64. 64.
    • Rapkin L, Pashankar FD. Management of thyroid carcinoma in children and young adults. J Pediatr Hematol Oncol. 2012;34 Suppl 2:S39–46. Review of well differentiated thyroid cancer and medullary thyroid cancer.PubMedCrossRefGoogle Scholar
  65. 65.
    DeLellis RA. Pathology and genetics of thyroid carcinoma. J Surg Oncol. 2006;94:662–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Grigsby PW, Gal-or A, Michalski JM, Doherty GM. Childhood and adolescent thyroid carcinoma. Cancer. 2002;95:724–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer. 2006;13:427–53.PubMedCrossRefGoogle Scholar
  68. 68.
    Stevens C, Lee JK, Sadatsafavi M, Blair GK. Pediatric thyroid fine-needle aspiration cytology: a meta-analysis. J Pediatr Surg. 2009;44:2184–91.PubMedCrossRefGoogle Scholar
  69. 69.
    Rachmiel M, Charron M, Gupta A, et al. Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma. J Pediatr Endocrinol Metab. 2006;19:1377–93.PubMedGoogle Scholar
  70. 70.
    Kiratli PO, Volkan-Salanci B, Günay EC, et al. Thyroid cancer in pediatric age group: an institutional experience and review of the literature. J Pediatr Hematol Oncol. 2013;35:93–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Tricoli JV, Seibel NL, Blair DG, et al. Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer. J Natl Cancer Inst. 2011;103:628–35.PubMedCrossRefGoogle Scholar
  72. 72.
    Pratt C. Management of infrequent tumors of childhood. In: Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 1149–76.Google Scholar
  73. 73.
    Compton C, Fenoglio-Preiser CM, Pettigrew N, et al. American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer. 2000;88:1739–57.PubMedCrossRefGoogle Scholar
  74. 74.
    Blanke CD, Bot BM, Thomas DM, et al. Impact of young age on treatment efficacy and safety in advanced colorectal cancer: a pooled analysis of patients from nine first-line phase III chemotherapy trials. J Clin Oncol. 2011;29(20):2781–6.PubMedCrossRefGoogle Scholar
  75. 75.
    el-Mawla NG, el-Bolkainy MN, Khaled HM. Bladder cancer in Africa: update. Semin Oncol. 2001;28:174–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Defoor W, Minevich E, Sheldon C. Unusual bladder masses in children. Urology. 2002;60:911.PubMedCrossRefGoogle Scholar
  77. 77.
    Paner GP, Zehnder P, Amin AM, et al. Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol. 2011;18:79–89.PubMedCrossRefGoogle Scholar
  78. 78.
    Kreuzer M, Kreienbrock L, Gerken M, et al. Risk factors for lung cancer in young adults. Am J Epidemiol. 1998;147:1028–37.PubMedCrossRefGoogle Scholar
  79. 79.
    Lal DR, Clark I, Shalkow J, et al. Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer. 2005;45:683–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRefGoogle Scholar
  81. 81.
    Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med. 2008;359:1367–80.PubMedCrossRefGoogle Scholar
  82. 82.
    Pavlidis N. Lung cancer during pregnancy: an emerging issue. Lung Cancer. 2008 Mar;59:279–81.Google Scholar
  83. 83.
    Sarıman N, Levent E, Yener NA, Orki A, Saygı A. Lung cancer and pregnancy. Lung Cancer. 2013;79:321–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carlos G. Ferreira
    • 1
  • Andréia Cristina de Melo
    • 2
  • Angélica Nogueira-Rodrigues
    • 2
  1. 1.Coordenação de Pesquisa Clínica e Incorporação Tecnológica, Coordenação Geral Tecnico-CientíficaINCA - Instituto Nacional de CâncerRio de JaneiroBrazil
  2. 2.INCA - Instituto Nacional de CâncerRio de JaneiroBrazil

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