Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 4/2009

01.04.2009 | Original Paper

HPV-16 E6 L83V variant in squamous cell carcinomas of the upper aerodigestive tract

verfasst von: Paolo Boscolo-Rizzo, Maria Cristina Da Mosto, Roberto Fuson, Helena Frayle-Salamanca, Rossana Trevisan, Annarosa Del Mistro

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of this prospective case series study was to determine the prevalence of HPV-DNA, analyze the E6 mRNA expression, identify intra-type variation in the E6 oncogene in upper aerodigestive tract (UADT) squamous cell carcinoma (SCC), and correlate the presence of HPV-DNA with several clinical parameters and outcome.

Methods

Frozen samples of UADT-SCC were analyzed for the presence and characterization of HPV-DNA and RNA sequences by means of polymerase chain reaction (PCR), reverse transcriptase-PCR, and direct sequencing of amplified products.

Results

HPV-DNA sequences were detected in 10% of the tumors, all of which were typed as HPV-16. Positivity for HPV-16 E6/E7 mRNA was observed in five of the eight HPV-positive tumors (62.5%). The HPV-16 E6 L83V variant was present in five cases. Multivariate analysis identified a history of absence of smoking (P = 0.009) as a predictor of HPV-positive tumor. No significant differences in overall and disease free survival curves were observed between patients with HPV-positive tumors and patients with tumors without detectable HPV-DNA.

Conclusion

Our findings support the etiological participation of HPV-16 in a subset of UADT-SCCs from patients lacking traditional risk factors. The potential prognostic significance of HPV-16 E6 L83V variant in HPV-16 positive UADT-SCCs should be more extensively investigated.
Literatur
Zurück zum Zitat Badaracco G, Rizzo C, Mafera B, Pichi B, Giannarelli D, Rahimi SS et al (2007) Molecular analyses and prognostic relevance of HPV in head and neck tumours. Oncol Rep 17:931–939PubMed Badaracco G, Rizzo C, Mafera B, Pichi B, Giannarelli D, Rahimi SS et al (2007) Molecular analyses and prognostic relevance of HPV in head and neck tumours. Oncol Rep 17:931–939PubMed
Zurück zum Zitat Barra S, Franceschi S, Negri E, Talamini R, La Vecchia C (1990) Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption. Int J Cancer 46:1017–1020. doi:10.1002/ijc.2910460612 PubMedCrossRef Barra S, Franceschi S, Negri E, Talamini R, La Vecchia C (1990) Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption. Int J Cancer 46:1017–1020. doi:10.​1002/​ijc.​2910460612 PubMedCrossRef
Zurück zum Zitat Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR et al (2004) Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst 96:998–1006PubMedCrossRef Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR et al (2004) Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst 96:998–1006PubMedCrossRef
Zurück zum Zitat Butz K, Geisen C, Ullmann A, Spitkovsky D, Hoppe-Seyler F (1996) Cellular responses of HPV-positive cancer cells to genotoxic anti-cancer agents: repression of E6/E7-oncogene expression and induction of apoptosis. Int J Cancer 68:506–513. doi:10.1002/(SICI)1097-0215(19961115)68:4<506::AID-IJC17>3.0.CO;2-2PubMedCrossRef Butz K, Geisen C, Ullmann A, Spitkovsky D, Hoppe-Seyler F (1996) Cellular responses of HPV-positive cancer cells to genotoxic anti-cancer agents: repression of E6/E7-oncogene expression and induction of apoptosis. Int J Cancer 68:506–513. doi:10.1002/(SICI)1097-0215(19961115)68:4<506::AID-IJC17>3.0.CO;2-2PubMedCrossRef
Zurück zum Zitat Charfi L, Jouffroy T, de Cremoux P, Le Peltier N, Thioux M, Fréneaux P et al (2008) Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome. Cancer Lett 260:72–78. doi:10.1016/j.canlet.2007.10.028 PubMedCrossRef Charfi L, Jouffroy T, de Cremoux P, Le Peltier N, Thioux M, Fréneaux P et al (2008) Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome. Cancer Lett 260:72–78. doi:10.​1016/​j.​canlet.​2007.​10.​028 PubMedCrossRef
Zurück zum Zitat Das BC, Sharma JK, Gopalakrishna V, Luthra UK (1992) Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions. J Gen Virol 73:2327–2336. doi:10.1099/0022-1317-73-9-2327 PubMedCrossRef Das BC, Sharma JK, Gopalakrishna V, Luthra UK (1992) Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions. J Gen Virol 73:2327–2336. doi:10.​1099/​0022-1317-73-9-2327 PubMedCrossRef
Zurück zum Zitat Del Mistro A, Bonaldi L, Bertorelle R, Minucci D, Franzetti M, Cattelan A et al (2001) Genital human papillomavirus types in immunocompetent and immunodepressed women in Northeast Italy: prevalence and cytomorphological correlations. J Low Genit Tract Dis 5:12–20. doi:10.1046/j.1526-0976.2001.51003.x PubMedCrossRef Del Mistro A, Bonaldi L, Bertorelle R, Minucci D, Franzetti M, Cattelan A et al (2001) Genital human papillomavirus types in immunocompetent and immunodepressed women in Northeast Italy: prevalence and cytomorphological correlations. J Low Genit Tract Dis 5:12–20. doi:10.​1046/​j.​1526-0976.​2001.​51003.​x PubMedCrossRef
Zurück zum Zitat Del Mistro A, Frayle-Salamanca H, Trevisan R, Bertorelle R, Parenti A, Bonoldi E et al (2006) Human papillomavirus typing of invasive cervical cancers in Italy. Infect Agent Cancer 1:9. doi:10.1186/1750-9378-1-9 PubMedCrossRef Del Mistro A, Frayle-Salamanca H, Trevisan R, Bertorelle R, Parenti A, Bonoldi E et al (2006) Human papillomavirus typing of invasive cervical cancers in Italy. Infect Agent Cancer 1:9. doi:10.​1186/​1750-9378-1-9 PubMedCrossRef
Zurück zum Zitat Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269. doi:10.1093/jnci/djn011 PubMedCrossRef Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269. doi:10.​1093/​jnci/​djn011 PubMedCrossRef
Zurück zum Zitat Ferris RL, Martinez I, Sirianni N, Wang J, López-Albaitero A, Gollin SM et al (2005) Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): a natural disease model provides insights into viral carcinogenesis. Eur J Cancer 41:807–815. doi:10.1016/j.ejca.2004.11.023 PubMedCrossRef Ferris RL, Martinez I, Sirianni N, Wang J, López-Albaitero A, Gollin SM et al (2005) Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): a natural disease model provides insights into viral carcinogenesis. Eur J Cancer 41:807–815. doi:10.​1016/​j.​ejca.​2004.​11.​023 PubMedCrossRef
Zurück zum Zitat Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720. doi:10.1093/jnci/92.9.709 PubMedCrossRef Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720. doi:10.​1093/​jnci/​92.​9.​709 PubMedCrossRef
Zurück zum Zitat Gillison ML, D’Souza G, Westra W, Sugar E, Xiao W, Begum S et al (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100:407–420. doi:10.1093/jnci/djn025 PubMedCrossRef Gillison ML, D’Souza G, Westra W, Sugar E, Xiao W, Begum S et al (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100:407–420. doi:10.​1093/​jnci/​djn025 PubMedCrossRef
Zurück zum Zitat Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM (2001) Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 92:805–813. doi:10.1002/1097-0142(20010815)92:4<805::AID-CNCR1386>3.0.CO;2-9PubMedCrossRef Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM (2001) Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 92:805–813. doi:10.1002/1097-0142(20010815)92:4<805::AID-CNCR1386>3.0.CO;2-9PubMedCrossRef
Zurück zum Zitat Muir C, Weiland L (1995) Upper aerodigestive tract cancers. Cancer 75(1 Suppl):147–153. doi:10.1002/1097-0142(19950101)75:1+<147::AID-CNCR2820751304>3.0.CO;2-UPubMedCrossRef Muir C, Weiland L (1995) Upper aerodigestive tract cancers. Cancer 75(1 Suppl):147–153. doi:10.1002/1097-0142(19950101)75:1+<147::AID-CNCR2820751304>3.0.CO;2-UPubMedCrossRef
Zurück zum Zitat Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C (2006) Cancer risk associated with alcohol and tobacco use: focus on upper aero-digestive tract and liver. Alcohol Res Health 29:193–198PubMed Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C (2006) Cancer risk associated with alcohol and tobacco use: focus on upper aero-digestive tract and liver. Alcohol Res Health 29:193–198PubMed
Zurück zum Zitat Pintos J, Franco EL, Black MJ, Bergeron J, Arella M (1999) Human papillomavirus and prognoses of patients with cancers of the upper aerodigestive tract. Cancer 85:1903–1909PubMed Pintos J, Franco EL, Black MJ, Bergeron J, Arella M (1999) Human papillomavirus and prognoses of patients with cancers of the upper aerodigestive tract. Cancer 85:1903–1909PubMed
Zurück zum Zitat Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121:1813–1820. doi:10.1002/ijc.22851 PubMedCrossRef Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121:1813–1820. doi:10.​1002/​ijc.​22851 PubMedCrossRef
Zurück zum Zitat Riethdorf S, Friedrich RE, Ostwald C, Barten M, Gogacz P, Gundlach KK et al (1997) p53 gene mutations and HPV infection in primary head and neck squamous cell carcinomas do not correlate with overall survival: a long-term follow-up study. J Oral Pathol Med 126:315–321. doi:10.1111/j.1600-0714.1997.tb00222.x CrossRef Riethdorf S, Friedrich RE, Ostwald C, Barten M, Gogacz P, Gundlach KK et al (1997) p53 gene mutations and HPV infection in primary head and neck squamous cell carcinomas do not correlate with overall survival: a long-term follow-up study. J Oral Pathol Med 126:315–321. doi:10.​1111/​j.​1600-0714.​1997.​tb00222.​x CrossRef
Zurück zum Zitat Sobin LH, Wittekind C (2002) TNM classification of malignant tumours, International Union Against Cancer, Geneva Sobin LH, Wittekind C (2002) TNM classification of malignant tumours, International Union Against Cancer, Geneva
Zurück zum Zitat Sturgis EM, Cinciripini PM (2007) Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110:1429–1435. doi:10.1002/cncr.22963 PubMedCrossRef Sturgis EM, Cinciripini PM (2007) Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110:1429–1435. doi:10.​1002/​cncr.​22963 PubMedCrossRef
Zurück zum Zitat Suligoi B, Cusan M, Santopadre P, Palù G, Catania S, Girelli G et al (2000) HSV-2 specific seroprevalence among various populations in Rome, Italy. The Italian Herpes Management Forum. Sex Transm Infect 76:213–214. doi:10.1136/sti.76.3.213 PubMedCrossRef Suligoi B, Cusan M, Santopadre P, Palù G, Catania S, Girelli G et al (2000) HSV-2 specific seroprevalence among various populations in Rome, Italy. The Italian Herpes Management Forum. Sex Transm Infect 76:213–214. doi:10.​1136/​sti.​76.​3.​213 PubMedCrossRef
Zurück zum Zitat Tommasino M (ed) (1997) Papillomaviruses in human cancer: the role of E6 and E7 oncoproteins. Molecular Biology Intelligence Unit series. Landes, Austin Tommasino M (ed) (1997) Papillomaviruses in human cancer: the role of E6 and E7 oncoproteins. Molecular Biology Intelligence Unit series. Landes, Austin
Zurück zum Zitat Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G et al (2004) Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol 74:117–126. doi:10.1002/jmv.20154 PubMedCrossRef Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G et al (2004) Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol 74:117–126. doi:10.​1002/​jmv.​20154 PubMedCrossRef
Zurück zum Zitat Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J et al (2006) Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24:736–747. doi:10.1200/JCO.2004.00.3335 PubMedCrossRef Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J et al (2006) Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24:736–747. doi:10.​1200/​JCO.​2004.​00.​3335 PubMedCrossRef
Metadaten
Titel
HPV-16 E6 L83V variant in squamous cell carcinomas of the upper aerodigestive tract
verfasst von
Paolo Boscolo-Rizzo
Maria Cristina Da Mosto
Roberto Fuson
Helena Frayle-Salamanca
Rossana Trevisan
Annarosa Del Mistro
Publikationsdatum
01.04.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0490-3

Weitere Artikel der Ausgabe 4/2009

Journal of Cancer Research and Clinical Oncology 4/2009 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

16.05.2024 Zielgerichtete Therapie Nachrichten

Trastuzumab deruxtecan scheint auch jenseits von Lungenkrebs gut gegen solide Tumoren mit HER2-Mutationen zu wirken. Dafür sprechen die Daten einer offenen Pan-Tumor-Studie.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.