Download PDF
Journal of Pediatric Neuroradiology 2016; 05(03): 221-228
DOI: 10.1055/s-0036-1593402
Review Article
Georg Thieme Verlag KG Stuttgart • New York

Increasing Incidence and Imaging in Pediatric Head and Neck Cancer and Role of the Human Papilloma Virus and Epstein–Barr Virus

Claudia F. E. Kirsch
1   Department of Radiology, Northwell Health, Hofstra Northwell School of Medicine, Manhasset, New York, United States
,
Gary Dellacerra
1   Department of Radiology, Northwell Health, Hofstra Northwell School of Medicine, Manhasset, New York, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
26 September 2016 (online)

    Permissions and Reprints

Abstract

Over the past few decades, the incidence of head and neck squamous cell carcinomas in the pediatric population and tumors associated with oncogenic human papilloma virus (HPV) has continued to increase. Previously, head and neck cancers in young patients were considered rare and—only in patients with genetic risk factors, with clinicians unaware of these neoplasms—occurring with greater frequency in younger patients, and often associated with HPV infection. This article reviews the viral oncogenic properties of HPV and Epstein–Barr virus, what the biomarker p16 represents, and the salient clinical and radiographic features of these tumors. Clinical awareness of these features is important to identify these tumors and initiate appropriate therapeutic treatment and to avoid any delay in diagnosis.

Keywords

human papilloma virus - Epstein–Barr virus - head and neck cancer - pediatric patients
 

  • References

  • 1 SEER Stat Fact Sheets: Oral Cavity and Pharynx Cancer . Available at: http://seer.cancer.gov/statfacts/html/oralcav.html . Accessed 2016
    PubMed
  • 2 Maier H, Weidauer H. Alcohol drinking and tobacco smoking are the chief risk factors for ENT tumors. Increased incidence of mouth cavity, pharyngeal and laryngeal carcinomas [in German]. Fortschr Med 1995; 113 (11) 157-160
    PubMedGoogle Scholar
  • 3 Schwartz I, Hughes C, Brigger MT. Pediatric head and neck malignancies: incidence and trends, 1973-2010. Otolaryngol Head Neck Surg 2015; 152 (6) 1127-1132
    CrossrefPubMedGoogle Scholar
  • 4 Reinhard H, Peters I, Gottschling S, Ebell W, Graf N. Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. J Pediatr Hematol Oncol 2007; 29 (7) 488-491
    CrossrefPubMedGoogle Scholar
  • 5 Young D, Xiao CC, Murphy B, Moore M, Fakhry C, Day TA. Increase in head and neck cancer in younger patients due to human papillomavirus (HPV). Oral Oncol 2015; 51 (8) 727-730
    CrossrefPubMedGoogle Scholar
  • 6 Tettamanti L, Caprioglio A, Tecco S , et al. Oral squamous cell carcinoma in the paediatric patient: a literature review. Eur J Paediatr Dent 2012; 13 (1) 35-40
    PubMedGoogle Scholar
  • 7 Sidell D, Nabili V, Lai C, Cheung G, Kirsch C, Abemayor E. Pediatric squamous cell carcinoma: case report and literature review. Laryngoscope 2009; 119 (8) 1538-1541
    CrossrefPubMedGoogle Scholar
  • 8 Albright JT, Topham AK, Reilly JS. Pediatric head and neck malignancies: US incidence and trends over 2 decades. Arch Otolaryngol Head Neck Surg 2002; 128 (6) 655-659
    CrossrefPubMedGoogle Scholar
  • 9 Cesmebasi A, Gabriel A, Niku D , et al. Pediatric head and neck tumors: an intra-demographic analysis using the SEER* database. Med Sci Monit 2014; 20: 2536-2542
    CrossrefPubMedGoogle Scholar
  • 10 Majchrzak E, Szybiak B, Wegner A , et al. Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature. Radiol Oncol 2014; 48 (1) 1-10
    CrossrefPubMedGoogle Scholar
  • 11 Toporcov TN, Znaor A, Zhang ZF , et al. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium. Int J Epidemiol 2015; 44 (1) 169-185
    CrossrefPubMedGoogle Scholar
  • 12 Kaminagakura E, Villa LL, Andreoli MA , et al. High-risk human papillomavirus in oral squamous cell carcinoma of young patients. Int J Cancer 2012; 130 (8) 1726-1732
    CrossrefPubMedGoogle Scholar
  • 13 Agalliu I, Gapstur S, Chen Z , et al. Associations of oral α-, β-, and γ-human papillomavirus types with risk of incident head and neck cancer. JAMA Oncol 2016; 2 (5) 599-606
    CrossrefPubMedGoogle Scholar
  • 14 Nelke KH, Lysenko L, Leszczyszyn J, Gerber H. Human papillomavirus and its influence on head and neck cancer predisposition. Postepy Hig Med Dosw (Online) 2013; 67: 610-616
    CrossrefPubMedGoogle Scholar
  • 15 van Monsjou HS, Wreesmann VB, van den Brekel MW, Balm AJ. Head and neck squamous cell carcinoma in young patients. Oral Oncol 2013; 49 (12) 1097-1102
    CrossrefPubMedGoogle Scholar
  • 16 Mallet Y, Avalos N, Le Ridant AM , et al. Head and neck cancer in young people: a series of 52 SCCs of the oral tongue in patients aged 35 years or less. Acta Otolaryngol 2009; 129 (12) 1503-1508
    CrossrefPubMedGoogle Scholar
  • 17 Bodner L, Manor E, Friger MD, van der Waal I. Oral squamous cell carcinoma in patients twenty years of age or younger—review and analysis of 186 reported cases. Oral Oncol 2014; 50 (2) 84-89
    CrossrefPubMedGoogle Scholar
  • 18 Chow CW, Tabrizi SN, Tiedemann K, Waters KD. Squamous cell carcinomas in children and young adults: a new wave of a very rare tumor?. J Pediatr Surg 2007; 42 (12) 2035-2039
    CrossrefPubMedGoogle Scholar
  • 19 Harris SL, Thorne LB, Seaman WT, Hayes DN, Couch ME, Kimple RJ. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck 2011; 33 (11) 1622-1627
    CrossrefPubMedGoogle Scholar
  • 20 Serraino D, Piselli P, Angeletti Cl, Scuderi M, Ippolito G, Capobianchi MR. Infection with Epstein-Barr virus and cancer: an epidemiological review. J Biol Regul Homeost Agents 2005; 19 (1–2) 63-70
    PubMedGoogle Scholar
  • 21 Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118 (12) 3030-3044
    CrossrefPubMedGoogle Scholar
  • 22 Rampias T, Sasaki C, Psyrri A. Molecular mechanisms of HPV induced carcinogenesis in head and neck. Oral Oncol 2014; 50 (5) 356-363
    CrossrefPubMedGoogle Scholar
  • 23 Chaturvedi AK, Engels EA, Pfeiffer RM , et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29 (32) 4294-4301
    CrossrefPubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 Prabhu SR, Wilson DF. Evidence of Epstein–Barr virus association with head and neck cancers: a review. J Can Dent Assoc 2016; 82 (g2): 1488-2159
    PubMedGoogle Scholar
  • 26 IARC (International Agency for Research on Cancer) Working Group on the Evaluation of Carcinogenic Risks to Humans. Nasopharyngeal carcinoma. In: Epstein-Barr Virus and Kaposi's Sarcoma Herpes Virus/Human Herpesvirus 8. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans 70. Lyon, France: IARC; 1997: 164-194
    Google Scholar
  • 27 Colevas AD. Population-based evaluation of incidence trends in oropharyngeal cancer focusing on socioeconomic status, sex, and race/ethnicity. Head Neck 2014; 36 (1) 34-42
    CrossrefPubMedGoogle Scholar
  • 28 Stein AP, Saha S, Yu M, Kimple RJ, Lambert PF. Prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in the United States across time. Chem Res Toxicol 2014; 27 (4) 462-469
    CrossrefPubMedGoogle Scholar
  • 29 Arbyn M, de Sanjosé S, Saraiya M , et al. EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease. Int J Cancer 2012; 131 (9) 1969-1982
    CrossrefPubMedGoogle Scholar
  • 30 zur Hausen H. Papillomaviruses in the causation of human cancers - a brief historical account. Virology 2009; 384 (2) 260-265
    CrossrefPubMedGoogle Scholar
  • 31 Iamaroon A, Pattanaporn K, Pongsiriwet S , et al. Analysis of 587 cases of oral squamous cell carcinoma in northern Thailand with a focus on young people. Int J Oral Maxillofac Surg 2004; 33 (1) 84-88
    CrossrefPubMedGoogle Scholar
  • 32 Ribeiro ACP, Silva AR, Simonato LE, Salzedas LM, Sundefeld ML, Soubhia AM. Clinical and histopathological analysis of oral squamous cell carcinoma in young people: a descriptive study in Brazilians. Br J Oral Maxillofac Surg 2009; 47 (2) 95-98
    CrossrefPubMedGoogle Scholar
  • 33 Krishna Rao SV, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade—an update (2000-2012). Asian Pac J Cancer Prev 2013; 14 (10) 5567-5577
    CrossrefPubMedGoogle Scholar
  • 34 Falaki F, Dalirsani Z, Pakfetrat A , et al. Clinical and histopathological analysis of oral squamous cell carcinoma of young patients in Mashhad, Iran: a retrospective study and review of literature. Med Oral Patol Oral Cir Bucal 2011; 16 (4) e473-e477
    PubMedGoogle Scholar
  • 35 Gaitán-Cepeda L-A, Peniche-Becerra A-G, Quezada-Rivera D. Trends in frequency and prevalence of oral cancer and oral squamous cell carcinoma in Mexicans. A 20 years retrospective study. Med Oral Patol Oral Cir Bucal 2011; 16 (1) e1-e5
    PubMedGoogle Scholar
  • 36 Bansal A, Singh MP, Rai B. Human papillomavirus-associated cancers: a growing global problem. Int J Appl Basic Med Res 2016; 6 (2) 84-89
    PubMedGoogle Scholar
  • 37 de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology 2004; 324 (1) 17-27
    CrossrefPubMedGoogle Scholar
  • 38 Bernard HU, Calleja-Macias IE, Dunn ST. Genome variation of human papillomavirus types: phylogenetic and medical implications. Int J Cancer 2006; 118 (5) 1071-1076
    CrossrefPubMedGoogle Scholar
  • 39 Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis. Ecancermedicalscience 2015; 9: 526
    PubMedGoogle Scholar
  • 40 Blitzer GC, Smith MA, Harris SL, Kimple RJ. Review of the clinical and biologic aspects of human papillomavirus-positive squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys 2014; 88 (4) 761-770
    CrossrefPubMedGoogle Scholar
  • 41 Gillison ML, Restighini C. Anticipation of the impact of human papillomavirus on clinical decision making for the head and neck cancer patient. Hematol Oncol Clin North Am 2015; 29 (6) 1045-1060
    CrossrefPubMedGoogle Scholar
  • 42 Mehanna H, Beech T, Nicholson T , et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck 2013; 35 (5) 747-755
    CrossrefPubMedGoogle Scholar
  • 43 International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 90. Lyon, France: World Health Organization; 2007: 223 , 670
    Google Scholar
  • 44 Ho L, Chan SY, Burk RD , et al. The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations. J Virol 1993; 67 (11) 6413-6423
    CrossrefPubMedGoogle Scholar
  • 45 Wood CE, Chen Z, Cline JM, Miller BE, Burk RD. Characterization and experimental transmission of an oncogenic papillomavirus in female macaques. J Virol 2007; 81 (12) 6339-6345
    CrossrefPubMedGoogle Scholar
  • 46 Chen Z, DeSalle R, Schiffman M, Herrero R, Burk RD. Evolutionary dynamics of variant genomes of human papillomavirus types 18, 45, and 97. J Virol 2009; 83 (3) 1443-1455
    CrossrefPubMedGoogle Scholar
  • 47 Harari A, Chen Z, Burk RD. Human papillomavirus genomics: past, present and future. Curr Probl Dermatol 2014; 45: 1-18
    PubMedGoogle Scholar
  • 48 Shope RE, Hurst EW. Infectious papillomatosis of rabbits: with a note on the histopathology. J Exp Med 1933; 58 (5) 607-624
    CrossrefPubMedGoogle Scholar
  • 49 Rous P, Beard JW. The progression to carcinoma of virus-induced rabbit papillomas (Shope). J Exp Med 1935; 62 (4) 523-548
    CrossrefPubMedGoogle Scholar
  • 50 Karamanou M, Agapitos E, Kousoulis A, Androutsos G. From the humble wart to HPV: a fascinating story throughout centuries. Oncol Rev 2010; 4 (3) 133-135
    CrossrefPubMedGoogle Scholar
  • 51 Aetios A, Olivieri A. Aetii Amideni Libri Medicinales I–VIII. Leipzig, Berlin: aedibus BG Teubneri; 1935
    Google Scholar
  • 52 Ciuffo G. Innesto positive con filtrato di verruca volgare. Giorn Ital Mal Venereol 1907; 48 (1) 12-17
    PubMedGoogle Scholar
  • 53 Rigoni-Stern D. Fatti statistici relative alle mallatie cancrosi che servirono de base alla poche cose dette dal dott. Giornale Service Propr Pathol Terap Ser 1842; 2: 507-517
    PubMedGoogle Scholar
  • 54 Gissmann L, Diehl V, Schultz-Coulon HJ, zur Hausen H. Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma. J Virol 1982; 44 (1) 393-400
    CrossrefPubMedGoogle Scholar
  • 55 Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnürch HG, zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A 1983; 80 (2) 560-563
    CrossrefPubMedGoogle Scholar
  • 56 Dürst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 1983; 80 (12) 3812-3815
    CrossrefPubMedGoogle Scholar
  • 57 Allison DB, Maleki Z. HPV-related head and neck squamous cell carcinoma: an update and review. J Am Soc Cytopathology 2016; 5 (4) 203-215
    PubMedGoogle Scholar
  • 58 Fakhry C, Westra WH, Li S , et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 2008; 100 (4) 261-269
    CrossrefPubMedGoogle Scholar
  • 59 Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 2010; 10 (8) 550-560
    CrossrefPubMedGoogle Scholar
  • 60 Grønhøj Larsen C, Gyldenløve M, Jensen DH , et al. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours: a systematic review. Br J Cancer 2014; 110 (6) 1587-1594
    CrossrefPubMedGoogle Scholar
  • 61 Langendijk JA, Psyrri A. The prognostic significance of p16 overexpression in oropharyngeal squamous cell carcinoma: implications for treatment strategies and future clinical studies. Ann Oncol 2010; 21 (10) 1931-1934
    CrossrefPubMedGoogle Scholar
  • 62 Kaka AS, Kumar B, Kumar P , et al. Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics. . Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 116 (3) 327-335
    CrossrefPubMedGoogle Scholar
  • 63 Zafereo ME, Xu L, Dahlstrom KR , et al. Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus. Oral Oncol 2016; 56: 47-53
    CrossrefPubMedGoogle Scholar
  • 64 Sedlacek TV, Lindheim S, Eder C , et al. Mechanism for human papillomavirus transmission at birth. Am J Obstet Gynecol 1989; 161 (1) 55-59
    CrossrefPubMedGoogle Scholar
  • 65 Syrjänen S. Current concepts on human papillomavirus infections in children. APMIS 2010; 118 (6–7) 494-509
    CrossrefPubMedGoogle Scholar
  • 66 Fredericks BD, Balkin A, Daniel HW, Schonrock J, Ward B, Frazer IH. Transmission of human papillomaviruses from mother to child. Aust N Z J Obstet Gynaecol 1993; 33 (1) 30-32
    CrossrefPubMedGoogle Scholar
  • 67 Rintala MA, Grénman SE, Järvenkylä ME, Syrjänen KJ, Syrjänen SM. High-risk types of human papillomavirus (HPV) DNA in oral and genital mucosa of infants during their first 3 years of life: experience from the Finnish HPV Family Study. Clin Infect Dis 2005; 41 (12) 1728-1733
    CrossrefPubMedGoogle Scholar
  • 68 Cason J, Kaye JN, Jewers RJ , et al. Perinatal infection and persistence of human papillomavirus types 16 and 18 in infants. J Med Virol 1995; 47 (3) 209-218
    CrossrefPubMedGoogle Scholar
  • 69 Syrjänen S, Puranen M. Human papillomavirus infections in children: the potential role of maternal transmission. Crit Rev Oral Biol Med 2000; 11 (2) 259-274
    CrossrefPubMedGoogle Scholar
  • 70 Syrjänen S. HPV infections and tonsillar carcinoma. J Clin Pathol 2004; 57 (5) 449-455
    CrossrefPubMedGoogle Scholar
  • 71 Perry ME, Jones MM, Mustafa Y. Structure of the crypt epithelium in human palatine tonsils. Acta Otolaryngol Suppl 1988; 454: 53-59
    PubMedGoogle Scholar
  • 72 Perry ME. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance. J Anat 1994; 185 (Pt 1): 111-127
    PubMedGoogle Scholar
  • 73 Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 2010; 11 (8) 781-789
    CrossrefPubMedGoogle Scholar
  • 74 Nelke KH, Lysenko L, Leszczyszyn J, Gerber H. Human papillomavirus and its influence on head and neck cancer predisposition. Postepy Hig Med Dosw (Online) 2013; 67: 610-616
    CrossrefPubMedGoogle Scholar
  • 75 Cantrell SC, Peck BW, Li G, Wei Q, Sturgis EM, Ginsberg LE. Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol 2013; 34 (10) 2005-2009
    CrossrefPubMedGoogle Scholar
  • 76 Corey AS, Hudgins PA. Radiographic imaging of human papillomavirus related carcinomas of the oropharynx. Head Neck Pathol 2012; 6 (1) (Suppl. 01) S25-S40
    CrossrefPubMedGoogle Scholar
  • 77 Trotta BM, Pease CS, Rasamny JJ, Raghavan P, Mukherjee S. Oral cavity and oropharyngeal squamous cell cancer: key imaging findings for staging and treatment planning. Radiographics 2011; 31 (2) 339-354
    CrossrefPubMedGoogle Scholar
  • 78 Stolk-Liefferink SAH, Dumans AG, van der Meij EH, Knegt PP, van der Wal KG. Oral squamous cell carcinoma in children; review of an unusual entity. Int J Pediatr Otorhinolaryngol 2008; 72 (1) 127-131
    CrossrefPubMedGoogle Scholar
  • 79 Moubayed SP, Chami R, Woods O, Olivier MJ, Dal Soglio DB, Lapointe A. Neonatal squamous cell carcinoma of the lip: case report and review of the literature. J Clin Oncol 2011; 29 (18) e549-e552
    CrossrefPubMedGoogle Scholar
  • 80 Rajkumar K, Perumal CJ, Singh AS, Hainsworth M. Squamous cell carcinoma of the upper lip in an 8 year old child-a case report. South African Dent J 2015; 70 (8) 360-363
    PubMedGoogle Scholar
  • 81 Morris LG, Patel SG, Shah JP, Ganly I. Squamous cell carcinoma of the oral tongue in the pediatric age group: a matched-pair analysis of survival. Arch Otolaryngol Head Neck Surg 2010; 136 (7) 697-701
    CrossrefPubMedGoogle Scholar
  • 82 Gronthos S, Brahim J, Li W , et al. Stem cell properties of human dental pulp stem cells. J Dent Res 2002; 81 (8) 531-535
    CrossrefPubMedGoogle Scholar
  • 83 Goldenberg D, Golz A, Netzer A , et al. Epstein-Barr virus and cancers of the head and neck. Am J Otolaryngol 2001; 22 (3) 197-205
    CrossrefPubMedGoogle Scholar
  • 84 Henle G, Henle W, Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A 1968; 59 (1) 94-101
    CrossrefPubMedGoogle Scholar
  • 85 zur Hausen H, Schulte-Holthausen H, Klein G , et al. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 1970; 228 (5276) 1056-1058
    CrossrefPubMedGoogle Scholar
  • 86 Metzger MJ, Villalba A, Carballal MJ , et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature 2016; 534 (7609) 705-709
    CrossrefPubMedGoogle Scholar
  • 87 Stambuk HE, Patel SG, Mosier KM, Wolden SL, Holodny AI. Nasopharyngeal carcinoma: recognizing the radiographic features in children. AJNR Am J Neuroradiol 2005; 26 (6) 1575-1579
    PubMedGoogle Scholar
  • 88 Tabuchi K, Nakayama M, Nishimura B, Hayashi K, Hara A. Early detection of nasopharyngeal carcinoma. Int J Otolaryngol 2011; 2011: 638058
    PubMedGoogle Scholar
  • 89 Makielski KR, Lee D, Lorenz LD , et al. Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes. Virology 2016; 495: 52-62
    CrossrefPubMedGoogle Scholar
  • 90 Young LS, Lau R, Rowe M , et al. Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. J Virol 1991; 65 (6) 2868-2874
    CrossrefPubMedGoogle Scholar
  • 91 Wolf H, zur Hausen H, Becker V. EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol 1973; 244 (138) 245-247
    PubMedGoogle Scholar