Abstract
Background
There is much evidence that high-risk human papillomavirus (HPV) plays a causative role in a subset of head and neck squamous cell cancer (HNSCC) in adults. HPV-positive tumors behave differently even in their response to treatment and are therefore a distinct subset. Both HPV-positive and HPV-negative tumors of the head and neck region are usually in the domain of adults and cases in children are rare; thus when a 2‑year-old child was diagnosed with this cancer in the external auditory canal, an in-depth assessment of the tumor was considered necessary.
Case report
A 2‑year-old girl was born to a HPV-positive mother who was diagnosed with cervical cancer during pregnancy. The child was delivered by caesarean section and the mother died of her cancer 7 months after delivery. After the diagnosis of locally invasive HPV-positive squamous cell cancer of the external auditory canal, the child was treated surgically, and with chemotherapy and radiotherapy. Full remission was obtained lasting up to 325 weeks since treatment was started, resulting in over 6 years of disease-free survival.
Conclusion
This is the first case of advanced, HPV-related HNSCC in a 2‑year-old child, in whom the tumor was located in the external auditory canal and who made a dramatic recovery after treatment with nonradical surgery, chemotherapy and radiotherapy. The child has currently been disease free for 6 years. This case supports the observation that HPV-related HNSCC tumors appear to respond favorably to treatment despite the patient’s young age and the clinically advanced stage of the tumor.
Zusammenfassung
Hintergrund
Es gibt reichlich Belege dafür, dass das menschliche Papillomavirus vom Hochrisikotyp (HR-HPV) in einigen Fällen von Plattenepithelkarzinomen des Kopf- und Halsbereichs (HNSCC) eine Schlüsselrolle spielt. HPV-positive Tumoren verhalten sich anders, auch bezüglich des Ansprechens auf die Behandlung. Deswegen stellen sie eine separate biologische Gruppe dar. Sowohl HPV-positive als auch HPV-negative Tumoren des Kopf- und Halsbereichs treten vor allem bei Erwachsenen auf und sind bei Kindern eine Seltenheit. Daher begründete die Diagnose eines Plattenepithelkarzinoms des äußeren Gehörgangs bei einem 2‑jährigen Kind die Notwendigkeit, die Krankheit eingehend zu untersuchen und zu beschreiben.
Fallbericht
Wir berichten über ein 2‑jähriges Mädchen, das von einer HPV-positiven Mutter geboren wurde, bei der während der Schwangerschaft Gebärmutterhalskrebs diagnostiziert worden war. Die Geburt erfolgte per Kaiserschnitt. Die Mutter erlag 7 Monate nach der Geburt ihrer Krebserkrankung. Das Kind wurde nach der Diagnose eines lokal fortgeschrittenen HPV-positiven Plattenepithelkarzinoms des äußeren Gehörgangs operativ und ergänzend mit Radio- und Chemotherapie behandelt. Erreicht wurde eine komplette Remission für mindestens 325 Wochen nach Beginn der Behandlung, sodass mehr als 6 Jahre keine Krankheitssymptome aufgetreten sind.
Schlussfolgerung
Dies ist die erste Fallbeschreibung eines stark fortgeschrittenen HR-HPV-positiven HNSCC des äußeren Gehörgangs bei einem 2‑jährigen Kind, bei dem nach Anwendung einer nichtradikalen chirurgischen Behandlung sowie einer Chemo- und Strahlentherapie eine spektakuläre Reaktion und ein aktuell 6‑jähriges krankheitsfreies Überleben erreicht wurden. Dieser Fall bestätigt die Beobachtungen, nach denen HNSCC-Tumoren im Zusammenhang mit HR-HPV günstig auf die Behandlung ansprechen – trotz des klinisch fortgeschrittenen Tumorstadiums und des jungen Patientenalters.
References
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35
Armbruster-Moraes E, Ioshimoto LM, Leão E, Zugaib M (1994) Presence of human papillomavirus DNA in amniotic fluids of pregnant women with cervical lesions. Gynecol Oncol 54:152–158
Cason J, Mant CA (2005) High-risk mucosal human papillomavirus infections during infancy & childhood. J Clin Virol 32(Supplement):52–58
Chaturvedi AK, Engels EA, Anderson WF, Gillison ML (2008) Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 26:612–619. doi:10.1200/JCO.2007.14.1713
Chera BS, Amdur RJ, Tepper J, Qaqish B, Green R, Aumer SL, Hayes N, Weiss J, Grilley-Olson J, Zanation A et al (2015) Phase 2 trial of de-intensified chemoradiation therapy for favorable-risk human papillomavirus – associated oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 93:976–985
Drolet M, Bénard É, Boily MC, Ali H, Baandrup L, Bauer H, Beddows S, Brisson J, Brotherton JM, Cummings T et al (2015) Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 15:565–580
El-Naggar AK, Westra WH (2012) p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck 34:459–461
Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, Lindsay BR, Kuter BJ, Perez G, Dominiak-Felden G et al (2016) Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of ten years of real-world experience. Clin Infect Dis 63:519–527. doi:10.1093/cid/ciw354
Gillison ML, Lowy DR (2004) A causal role for human papillomavirus in head and neck cancer. Lancet 363:1488–1489
Hammarstedt L, Lindquist D, Dahlstrand H et al (2006) Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer 119:2620–2623. doi:10.1002/ijc.22177
Heiduschka G, Grah A, Oberndorfer F, Kadletz L, Altorjai G, Kornek G, Wrba F, Thurnher D, Selzer E (2014) Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy. Strahlenther Onkol 191:209–216
Huang SH, Perez-Ordonez B, Weinreb I, Hope A, Massey C, Waldron JN, Kim J, Bayley AJ, Cummings B, John Cho BC et al (2013) Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol 49:79–85
Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J (2009) Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 27:1992–1998. doi:10.1200/jco.2008.20.2853
Lobo D, Llorente JL, Suárez C (2008) Squamous cell carcinoma of the external auditory canal. Skull Base 18:167–172
Madsen AR, Gundgaard MG, Hoff CM, Maare C, Holmboe P, Knap M, Thomsen LL, Buchwald C, Hansen HS, Bretlau P et al (2008) Cancer of the external auditory canal and middle ear in Denmark from 1992 to 2001. Head Neck 30:1332–1338
Mammas IN, Sourvinos G, Spandidos DA (2009) Human papilloma virus (HPV) infection in children and adolescents. Eur J Pediatr 168:267–273
van Monsjou HS, Wreesmann VB, van den Brekel MWM, Balm AJM (2013) Head and neck squamous cell carcinoma in young patients. Oral Oncol 49:1097–1102
O’Sullivan B, Huang SH, Perez-Ordonez B, Massey C, Siu LL, Weinreb I, Hope A, Kim J, Bayley AJ, Cummings B et al (2012) Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol 103:49–56
Pakarian F, Kaye J, Cason J, Kell B, Jewers R, Derias NW, Raju KS, Best JM (1994) Cancer associated human papillomaviruses: perinatal transmission and persistence. Br J Obstet Gynaecol 101:514–517
Puranen M, Yliskoski M, Saarikoski S, Syrjänen K, Syrjänen S (1996) Vertical transmission of human papillomavirus from infected mothers to their newborn babies and persistence of the virus in childhood. Am J Obstet Gynecol 174:694–699
Rades D, Seibold ND, Gebhard MP, Noack F, Thorns C, Schild SE (2013) Impact of the HPV-positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck. Strahlenther Onkol 189:856–860
Rintala MAM, Grénman SE, Puranen MH, Isolauri E, Ekblad U, Kero PO, Syrjänen SM (2005) Transmission of High-Risk Human Papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland. J Clin Microbiol 43:376–381
Rombaldi RL, Serafini EP, Mandelli J, Zimmer-mann E, Losquiavo KP (2008) Transplacental trans-mission of human papillomavirus. Virol J 5:106–120
Sarkola ME, Grenman SE, Rintala MA, Syrja-nen KJ, Syrjanen SM (2008) Human papillomavirus inthe placenta and umbilical cord blood. Acta Obstet Gynecol Scand 87:1181–1188
Smeets SJ, Hesselink AT, Speel E‑JM, Haesevoets A, Snijders PJF, Pawlita M, Meijer CJLM, Braakhuis BJM, Leemans CR, Brakenhoff RH (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472
Syrjänen S (2010) Current concepts on human papillomavirus infections in children. APMIS 118:494–509
Syrjanen S, Puranen M (2000) Human papillomavirus infections in children: the potential role of maternal transmission. Crit Rev Oral Biol Med 11:259–274
Testa JG, Fukuda Y, Kowalski LP (1997) Prognostic factors in carcinoma of the external auditory canal. Arch Otolaryngol Head Neck Surg 123:720–724
Tseng CJ, Lin CY, Wang RL, Chen LJ, Chang YL, Hsieh TT, Pao CC (1992) Possible transplacental transmission of human papillomaviruses. Am J Obstet Gynecol 166:35–40
Visnyei K, Gill R, Azizi E, Culliney B (2013) Squamous cell carcinoma of the external auditory canal: a case report and review of the literature. Oncol Lett 5:1587–1590
World Health Organization (2013) Countries with HPV vaccine in the national immunisation programme and planned introductions. http://www.who.int/immunization/diseases/hpv/decision_implementation/en/. Accessed on 14.03.2016
Zhang T, Dai C, Wang Z (2013) The misdiagnosis of external auditory canal carcinoma. Eur Arch Otorhinolaryngol 270:1607–1613
Acknowledgements
We are grateful to Dr Donald Roberts, Associate Professor, (Sahlgrenska University Hospital, Gothenburg, Sweden) and Dr Tomasz Rutkowski, Associate Professor, (I Radiation and Clinical Oncology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch) for scientific comments and editorial support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
M. Snietura, L. Chelmecka-Wiktorczyk, Sr. Pakulo, A. Kopec, W. Piglowski, G. Drabik, B. Kosowski, L. Wyrobek, A. Stanek-Widera and W. Balwierz state that they have no competing interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Snietura, M., Chelmecka-Wiktorczyk, L., Pakulo, S. et al. Vertically transmitted HPV-dependent squamous cell carcinoma of the external auditory canal. Strahlenther Onkol 193, 156–161 (2017). https://doi.org/10.1007/s00066-016-1047-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-016-1047-z