Table Of ContentRecent Results in Cancer Research
Series Editors: P. M. Schlag · H.-J. Senn
Wojciech Golusiński
René Leemans
Andreas Dietz E ditors
HPV
Infection in
Head and
Neck Cancer
Recent Results in Cancer Research
Volume 206
Series editors
P.M. Schlag, Berlin, Germany
H.-J. Senn, St. Gallen, Switzerland
Associate Editors
P. Kleihues, Zürich, Switzerland
F. Stiefel, Lausanne, Switzerland
B. Groner, Frankfurt, Germany
A. Wallgren, Göteborg, Sweden
Founding Editor
P. Rentchnik, Geneva, Switzerland
More information about this series at http://www.springer.com/series/392
Wojciech Golusiński C. René Leemans
(cid:129)
Andreas Dietz
Editors
HPV Infection in Head
and Neck Cancer
123
Editors
Wojciech Golusiński Andreas Dietz
Department ofHead andNeck Surgery Department ofHead Medicine andOral
TheGreater PolandCancer Centre Health,Clinic of Otolaryngology
Poznan University of Medical Sciences University of Leipzig
Poznań Leipzig
Poland Germany
C. RenéLeemans
Department ofOtolaryngology-Head
andNeckSurgery
VUUniversity Medical Center/Cancer
CenterAmsterdam
Amsterdam
TheNetherlands
ISSN 0080-0015 ISSN 2197-6767 (electronic)
Recent Resultsin Cancer Research
ISBN978-3-319-43578-7 ISBN978-3-319-43580-0 (eBook)
DOI 10.1007/978-3-319-43580-0
LibraryofCongressControlNumber:2016947932
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Contents
Part I Epidemiology and Molecular Biology of HPV
Positive HNSCC
HPV in Head and Neck Cancer—30 Years of History. . . . . . . . . . . . . 3
Stina Syrjänen, Jaana Rautava and Kari Syrjänen
Epidemiology of HPV-Positive Tumors in Europe
and in the World. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Xavier Castellsagué, Marisa Mena and Laia Alemany
Molecular Patterns and Biology of HPV-Associated HNSCC. . . . . . . . 37
Ruud H. Brakenhoff, Steffen Wagner and Jens P. Klussmann
HPV Integration in Head and Neck Squamous Cell Carcinomas:
Cause and Consequence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Ernst Jan M. Speel
Risk Factors for Oral Infection with Human Papillomavirus. . . . . . . . 73
Pawel Golusinski
Part II HPV Testing
HPV-Related Head and Neck Squamous Cell Carcinomas. . . . . . . . . . 89
Andrzej Marszałek and Łukasz Szylberg
HPV Testing of Head and Neck Cancer in Clinical Practice . . . . . . . . 101
Max Robinson
Variation of HPV Subtypes with Focus on HPV-Infection
and Cancer in the Head and Neck Region . . . . . . . . . . . . . . . . . . . . . 113
Gunnar Wichmann
Tumor Staging and HPV-Related Oropharyngeal Cancer . . . . . . . . . . 123
Claus Wittekindt and Jens Peter Klussmann
v
vi Contents
Part III Non-Surgical Treatment of HPV Positive Tumours
Human Papillomavirus (HPV): A Criterion for Therapeutic
Decision in Squamous Cell Carcinoma of the Head and Neck? . . . . . . 137
Jan B. Vermorken
Systemic Treatment in HPV-Induced Recurrent
or Metastatic HNSCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Damian T. Rieke and Ulrich Keilholz
Optimizing Radiotherapy in HPV-Associated
Oropharyngeal Cancer Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Johannes A. Langendijk and Roel J.H.M. Steenbakkers
Should We De-escalate the Treatment for HPV-Positive Tumors? . . . . 173
Andreas Dietz, Gunnar Wichmann and Susanne Wiegand
Part IV Surgical Treatment of HPV Positive Tumours
The Role of Conventional Surgery in Oropharyngeal Cancer . . . . . . . 185
Wojciech Golusinski
The Role of Surgery in the Management of Recurrent
Oropharyngeal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Neil D. Gross and Ehab Y. Hanna
TORS in HPV-Positive Tumors—The New Standard?. . . . . . . . . . . . . 207
S. Lang, S. Mattheis and B. Kansy
Part V Predictive Factors for Outcome and Quality of Life
in HPV Positive and HPV Negative
Risk Groups for Survival in HPV-Positive
and HPV-Negative OPSCC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Michelle M. Rietbergen, Ruud H. Brakenhoff and C. René Leemans
Predictive Factors for Outcome and Quality of Life
in HPV-Positive and HPV-Negative HNSCC. . . . . . . . . . . . . . . . . . . . 233
Jochen Hess
Cancer Immunology and HPV. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Barbara Wollenberg
Part VI HPV - Prevention Vaccination, Ongoing Trials
Update on De-intensification and Intensification Studies in HPV . . . . . 251
Hisham Mehanna
Vaccination Expectations in HNSCC . . . . . . . . . . . . . . . . . . . . . . . . . 257
Stina Syrjänen and Jaana Rautava
Part I
Epidemiology and Molecular Biology of
HPV Positive HNSCC
HPV in Head and Neck Cancer—
30 Years of History
Stina Syrjänen, Jaana Rautava and Kari Syrjänen
Abstract
The interesting history of papillomavirus (PV) research has been reviewed
before. The history of human papillomavirus (HPV) in head and neck region
startsin1901whenthecontagioustransmissionofwartylesionsintothemouth
viaoral sexwasdescribed, althoughtheconfirmationoftheirviraletiology had
to wait until 1907. Ullman was the first to associate the human wart virus with
laryngeal warts. Parsons and Kidd described the natural history of oral PV
infections in rabbits already in 1942, but these findings were corroborated in
humansonlyrecently.KoilocytoticatypiadescribedbyKossandDurfeein1956
was recognized as asign ofHPV infection in cervicalprecancer lesions onlyin
1976–1977 (Meisels and Fortin; Purola and Savia). This prompted systematic
surveys of head and neck lesions for the detection of koilocytosis since the late
1970s,andtheauthorsofthiscommunicationwerethefirsttoproposetheHPV
involvement in a subgroup of head and neck cancers. Brandsma and Abramson
demonstrated HPV16 DNA in tonsillar SCCs in 1989. Since the early 2000s,
HPV research of head and neck squamous cell carcinomas (HNSCC) has made
impressiveprogress,confirmingthatthespecificanatomicsiteplaysakeyrolein
determining the susceptibility to HPV infection. The most likely cancer sites
associatedwithHPVarethebaseofthetongueandpalatinetonsils,followedby
S.Syrjänen(&)(cid:1)J.Rautava
DepartmentofOralPathology,FacultyofMedicine,InstituteofDentistry,
UniversityofTurku,Lemminkäisenkatu2,20520Turku,Finland
e-mail:stina.syrjanen@utu.fi
S.Syrjänen(cid:1)J.Rautava
DepartmentofPathology,TurkuUniversityHospital,UniversityofTurku,
Turku,Finland
K.Syrjänen
DepartmentofClinicalResearch,BiohitOyj,Helsinki,Finland
©SpringerInternationalPublishingSwitzerland2017 3
W.Golusińskietal.(eds.),HPVInfectioninHeadandNeckCancer,
RecentResultsinCancerResearch206,DOI10.1007/978-3-319-43580-0_1
4 S.Syrjänenetal.
oral cavity, larynx, and sinonasal mucosa. There is substantial geographic
variation in HPV association with HNSCC. Patients with HPV-associated
HNSCC are younger, and survival is better than in the absence of HPV.
Keywords
(cid:1) (cid:1)
History Human papillomavirus (HPV) Head and neck squamous cell
carcinomas (HNSSC)
1 Introduction
Thepresent-dayunderstandingofpapillomavirus(PV)researchisaresultofalong
history of intense work consisting of important innovations and contributions of a
countless number of past and present scientists. The past history of PV research is
dual consisting of (1) basic virology research, and (2) an increasing awareness of
human papillomaviruses (HPV) as a significant cause of human diseases emerging
from the late 1970s. Several excellent reviews exist on the history of PV research
(Syverton et al. 1950; Bäfverstedt 1967; Grodzicker and Hopkins, Oriel in 1989;
LancasterandOlson1982;Gross1983;Orth1986;Oriel1989;zurHausenandde
Villiers 1994; Lowy and Schiller 2006; Syrjänen and Syrjänen 2008; zur Hausen
2009). Since the early 2000s, the studies on HPV and head and neck cancer have
increased overwhelmingly.
ThischaptersummarizesshortlythemainmilestonesoftheHPVresearchwhich
havemadeanimpactinthestepwiseunderstandingofHPVasanetiologicalagent
in a subgroup of head and neck squamous cell carcinomas (HNSCC). One has to
note that this type oflistingrepresents thepersonalpreferences of theauthors,and
the missing of someone’s name in the list by no means signifies the lack of
importance of their work. The head and neck region discussed here comprises a
number of distinct anatomic sites including oral cavity, nasal cavity, paranasal
sinuses,nasopharynx,oropharynx,hypopharynx,andlarynx.Thishistoricalreview
ontheroleofHPVinheadandneckcancersisspecificallyacknowledgingtheearly
papers published during the next 10 years after the original observations and is
summarized in the Tables 1, 2, 3, and 4.
Table1 DetectionofHPVinoralcarcinomasduringthefirst10yearsaftertheoriginalreport
Reference Lesion No.ofcases Method HPV-positivity Typesdetected
Syrjänenetal. SCC 40 ICH 8/40 20%
(1983a,b,c,d)
Syrjänenetal. SCC 1 ICH 0/1 0%
(1983a,b,c,d)
Syrjänenetal. SCC 6 ICH 0/6 0%
(1983a,b,c,d)
(continued)
