HPV-positive oropharyngeal cancer

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HPV-positive oropharyngeal cancer
Classification and external resources
Hpv positive tumor in situ hybridization.png
HPV positive HNSCC (in situ hybridization)
ICD-10 C09.0-C10.9
C01,C02.4,C14.2

Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) also known as HPV16+ oropharyngeal cancer or HPV+ OPC is a recognized subtype of Oropharyngeal squamous cell carcinomas (OSCC),[1][2][3] associated with the HPV type 16 virus.

Causes[edit]

HPV oral infection precedes the development of HPV+ OPC.[4][5] Slight injuries in the mucous membrane serve as an entry gate for HPV, which thus works into the basal layer of the epithelium.[6][7] People testing positive for HPV16 oral infection have a 14 times increased risk of developing HPV+ OPC.[6]

Immunosuppression seems to be an increased risk factor for HPV+ OPC.[5] Individuals with TGF-β1 genetic variations, specially T869C, are more likely to have HPV16+ OPC.[8] TGF-β1 plays an important role in controlling the immune system.

A 1999 study has found that patients with human papillomavirus (HPV)-associated anogenital cancers had a 4.3-fold increased risk of tonsillar squamous-cell carcinoma.[9]

Although evidence suggests that HPV16 is the main cause of OPC between non-smokers and non-drinkers, the degree to which tobacco and/or alcohol use may contribute to increase the risk of HPV+ OPC is unclear.[5]

Concomitant human herpesvirus-8 infection can potentiate the effects of HPV-16.[10]

Mechanism[edit]

A prospective study has found that increased HPV+ OPC risk was observed more than 15 years after HPV exposure,[4] pointing to a slow development of the disease, like in cervical cancer.

HPV associated cancers are caused by the expression of HPV's E6 and E7 proteins that bind to and inactivate tumor suppressor proteins p53 and retinoblastoma protein (pRB), respectively, leading to malignant transformation of HPV infected cells.[4][11]

The biology of HPV+ OPC is distinct of HPV- OPC with P53 degradation (inactivated by E6 instead of by genetic mutation), pRB pathway inactivation (by E7 instead of Cyclin D1 amplification), and P16 upregulation (over-expression of p16 instead of inactivation due to reduced negative feedback from pRB).[12][13]

The tonsils epithelia (palatine and lingual) share similar nonkeratinization characteristic with the cervix, where HPV infection play the major role in cases of cervical cancer.[6][14]

Diagnosis[edit]

HPV+ OPC is usually diagnosed at a more advanced stage than HPV- OPC.[4]

Genetic signatures of HPV+ and HPV- OPC are different.[15][16][17][18][19]

HPV OPC is associated with expression level of the E6/E7 mRNAs and of p16.[20] Nonkeratinizing squamous cell carcinoma strongly predicts HPV-association.[21][22]

HPV OPC is not merely characterized by the presence of HPV-16. Only the expression of viral oncogenes within the tumor cells plus the serum presence of E6 or E7 antibodies is unambiguously conclusive.[6]

There's not a standard HPV testing method in head and neck cancers,[23] both in situ hybridization and PCR are commonly used.[12][24] A 2010 study has concluded that both have comparable performance for HPV detection, however it's important to use appropriate sensitivity controls.[25]

Prevention[edit]

Risk factors are high number of sexual partners,[26][27][28] (25% increase >= 6 partners)[29] history of oral-genital sex,[27][28] (125% >= 4 partners)[29] history of anal–oral sex,[27] female partner had a history of either an abnormal Pap smear or a cervical dysplasia,[27][30] chronic periodontitis,[31][32] and, among men, decreasing age at first intercourse[26] and history of genital warts.[26]

A 2010 study concluded that current tobacco users with advanced HPV+ OSCC are at higher risk of disease recurrence compared with never-tobacco users.[33]

HPV vaccines have a theoretical potential to prevent oral HPV infection.[4]

A 2010 review study has found that HPV16 oral infection was rare (1.3%) among the 3,977 healthy subjects analyzed.[34]

Treatment[edit]

Currently HPV+ OPC are treated similarly to stage-matched and site-matched unrelated OPC. However less intensive use of radiotherapy or chemotherapy, as well as specific therapy, is under research.[3][35]

It's hypothesized that HPV+ OPC patients benefit better from radiotherapy and concurrent cetuximab treatment than HPV- OPC patients receiving the same treatment.[36]

Prognosis[edit]

Tumor HPV status is strongly associated with positive therapeutic response and survival compared with HPV-negative OPC.[37][38][39] A possible explanation is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease"[6] Presence of TP53 mutations, a marker for HPV- OPC, is associated with worse prognosis.[4]

High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response.[24]

Epidemiology[edit]

HPV+ OPC patients tend to be younger than HPV- patients.[40] Currently in the US there is a growing incidence of HPV associated oropharyngeal cancers,[41][42][43] perhaps as a result of changing sexual behaviors.[44][45] Tonsil and oropharyngeal cancers increased in male predominance between 1975 and 2004, despite reductions in smoking.[46] The decline in smoking may be linked to the decreasing proportion of HPV negative cancers, while changes in sexual activity may be reflected in increasing proportion of HPV positive cancers.[47] Recently, in the US, HPV associated OPC represent about 60% of OPC cases[37][48][49] compared with 40% in the previous decade.[49] By 2007, in the US, incidence of general OPC, including non-HPV associated, is 3.2 cases per 100,000 males/year and 1.9 per 100,000 all-sexes/year.[50]

The higher increase incidence of HPV associated OPC is also seen in other countries, like Sweden, with a 2007 incidence of over 80% for cancer in the tonsils,[51][52] Finland[53] and Czech Republic.[54]

In Australia incidence of HPV associated OPC is 1.56 cases per 100,000 males/year.[55]

History[edit]

In 1983, it was first suggested[5] that HPV might be the agent involved in the development of at least certain special types of oral cancers.[56] In 2007 the World Health Organization stated HPV was a cause for oral cancers.[4][57]

References[edit]

  1. ^ Westra, W. H. (2009). "The Changing Face of Head and Neck Cancer in the 21st Century: the Impact of HPV on the Epidemiology and Pathology of Oral Cancer". Head and Neck Pathology 3 (1): 78–81. doi:10.1007/s12105-009-0100-y. PMC 2807531. PMID 20596995.  edit
  2. ^ Gillison, M. L.; Koch, W. M.; Capone, R. B.; Spafford, M.; Westra, W. H.; Wu, L.; Zahurak, M. L.; Daniel, R. W.; Viglione, M.; Symer, D. E.; Shah, K. V.; Sidransky, D. (May 2000). "Evidence for a causal association between human papillomavirus and a subset of head and neck cancers" (Free full text). Journal of the National Cancer Institute 92 (9): 709–720. doi:10.1093/jnci/92.9.709. ISSN 0027-8874. PMID 10793107.  edit
  3. ^ a b Psyrri, A.; Gouveris, P.; Vermorken, J. B. (2009). "Human papillomavirus-related head and neck tumors: clinical and research implication". Current Opinion in Oncology 21 (3): 201–205. doi:10.1097/CCO.0b013e328329ab64. PMID 19370803.  edit
  4. ^ a b c d e f g Chaturvedi, Anil; Maura L. Gillison (March 4, 2010). "Human Papillomavirus and Head and Neck Cancer". In Andrew F. Olshan. Epidemiology, Pathogenesis, and Prevention of Head and Neck Cancer (1st ed.). New York: Springer. ISBN 978-1-4419-1471-2. 
  5. ^ a b c d Mannarini, L.; Kratochvil, V.; Calabrese, L.; Gomes Silva, L.; Morbini, P.; Betka, J.; Benazzo, M. (2009). "Human Papilloma Virus (HPV) in head and neck region: review of literature". Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale 29 (3): 119–126. PMC 2815356. PMID 20140157.  edit
  6. ^ a b c d e Michl, P; Pazdera, J; Prochazka, M; Pink, R; Stosova, T (2010). "Human papillomavirus in the etiology of head and neck carcinomas" (PDF). Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 154 (1): 9–12. PMID 20445705.  edit
  7. ^ Vidal, L.; Gillison, M. (2008). "Human papillomavirus in HNSCC: recognition of a distinct disease type". Hematology/oncology clinics of North America 22 (6): 1125–1142, vii. doi:10.1016/j.hoc.2008.08.006. PMID 19010263.  edit
  8. ^ Guan, X.; Sturgis, E.; Lei, D.; Liu, Z.; Dahlstrom, K.; Wei, Q.; Li, G. (2010). "Association of TGF-beta1 genetic variants with HPV16-positive oropharyngeal cancer". Clinical Cancer Research 16 (5): 1416–1422. doi:10.1158/1078-0432.CCR-09-2877. PMC 2831118. PMID 20179236.  edit
  9. ^ Frisch, M.; Biggar, R. (1999). "Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas". The Lancet 354 (9188): 1442. doi:10.1016/S0140-6736(99)92824-6.  edit
  10. ^ Underbrink, M.; Hoskins, S.; Pou, A.; Albrecht, T. (2008). "Viral interaction: a possible contributing factor in head and neck cancer progression". Acta Oto-Laryngologica 128 (12): 1361–1369. doi:10.1080/00016480801965001. PMID 18607925.  edit
  11. ^ Smeets, S.; Van Der Plas, M.; Schaaij-Visser, T.; Van Veen, E.; Van Meerloo, J.; Braakhuis, B.; Steenbergen, R.; Brakenhoff, R. (2010). "Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways". International Journal of Cancer. Journal International Du Cancer 128 (7): n/a. doi:10.1002/ijc.25474. PMID 20499310.  edit
  12. ^ a b Marur, S.; D'souza, G.; Westra, W. H.; Forastiere, A. A. (2010). "HPV-associated head and neck cancer: a virus-related cancer epidemic". The Lancet Oncology 11 (8): 781–789. doi:10.1016/S1470-2045(10)70017-6. PMID 20451455.  edit
  13. ^ Hunt, Jennifer L. (25 February 2010). "Molecular Assessment of HPV in Patients with Head and Neck Tumors" (PDF). Retrieved 13 May 2010. 
  14. ^ Salem, A. (2010). "Dismissing links between HPV and aggressive tongue cancer in young patients". Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 21 (1): 13–17. doi:10.1093/annonc/mdp380. PMID 19825879.  edit
  15. ^ Klussmann, J.; Mooren, J.; Lehnen, M.; Claessen, S.; Stenner, M.; Huebbers, C.; Weissenborn, S.; Wedemeyer, I.; Preuss, S.; Straetmans, J. M. J. A. A.; Manni, J. J.; Hopman, A. H. N.; Speel, E. -J. M. (Mar 2009). "Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications". Clinical Cancer Research 15 (5): 1779–1786. doi:10.1158/1078-0432.CCR-08-1463. ISSN 1078-0432. PMID 19223504.  edit
  16. ^ Lohavanichbutr, P.; Houck, J.; Fan, W.; Yueh, B.; Mendez, E.; Futran, N.; Doody, D.; Upton, M.; Farwell, D.; Schwartz, S. M.; Zhao, L. P.; Chen, C. (Feb 2009). "Genome-wide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices". Archives of Otolaryngology—Head & Neck Surgery 135 (2): 180–188. doi:10.1001/archoto.2008.540. ISSN 0886-4470. PMC 2761829. PMID 19221247.  edit
  17. ^ Schlecht, N.; Burk, R.; Adrien, L.; Dunne, A.; Kawachi, N.; Sarta, C.; Chen, Q.; Brandwein-Gensler, M.; Prystowsky, M.; Childs, G.; Smith, R. V.; Belbin, T. J. (Nov 2007). "Gene expression profiles in HPV-infected head and neck cancer". The Journal of pathology 213 (3): 283–293. doi:10.1002/path.2227. ISSN 0022-3417. PMID 17893858.  edit
  18. ^ Weinberger, P.; Yu, Z.; Kountourakis, P.; Sasaki, C.; Haffty, B.; Kowalski, D.; Merkley, M.; Rimm, D.; Camp, R.; Psyrri, A. (Sep 2009). "Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: Validation of three-class hypothesis". Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 141 (3): 382–389.e1. doi:10.1016/j.otohns.2009.04.014. ISSN 0194-5998. PMID 19716018.  edit
  19. ^ Martinez, I.; Wang, J.; Hobson, K.; Ferris, R.; Khan, S. (Jan 2007). "Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas". European journal of cancer (Oxford, England : 1990) 43 (2): 415–432. doi:10.1016/j.ejca.2006.09.001. ISSN 0959-8049. PMC 1847595. PMID 17079134.  edit
  20. ^ Jung, A.; Briolat, J.; Millon, R.; De Reyniès, A.; Rickman, D.; Thomas, E.; Abecassis, J.; Clavel, C.; Wasylyk, B. (2009). "Biological and clinical relevance of transcriptionnally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma". International Journal of Cancer. Journal International Du Cancer 126 (8): 1882–1894. doi:10.1002/ijc.24911. PMID 19795456.  edit
  21. ^ Chernock, R. D.; El-mofty, S. K.; Thorstad, W. L.; Parvin, C. A.; Lewis, J. S. (2009). "HPV-Related Nonkeratinizing Squamous Cell Carcinoma of the Oropharynx: Utility of Microscopic Features in Predicting Patient Outcome". Head and Neck Pathology 3 (3): 186–194. doi:10.1007/s12105-009-0126-1. PMC 2811624. PMID 20596971.  edit
  22. ^ Elmofty, S.; Patil, S. (2006). "Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: Characterization of a distinct phenotype". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 101 (3): 339–345. doi:10.1016/j.tripleo.2005.08.001. PMID 16504868.  edit
  23. ^ Robinson, M.; Sloan, P.; Shaw, R. (2010). "Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing.". Oral oncology 46 (7): 492–496. doi:10.1016/j.oraloncology.2010.02.013. PMID 20227331.  edit
  24. ^ a b Munck-Wikland, Eva; Hammarstedt, Lalle; Dahlstrand, Hanna (2010). "Role of Human Papillomavirus in Tonsillar Cancer". In M. A. Hayat. Methods of Cancer Diagnosis, Therapy, and Prognosis 7. Springer. pp. 271–283. ISBN 978-90-481-3185-3. 
  25. ^ Agoston, E. .; Robinson, S. .; Mehra, K. .; Birch, C. .; Semmel, D. .; Mirkovic, J. .; Haddad, R. .; Posner, M. .; Kindelberger, D. .; Krane, J. F.; Brodsky, J.; Crum, C. P. (2010). "Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx". American journal of clinical pathology 134 (1): 36–41. doi:10.1309/AJCP1AAWXE5JJCLZ. PMID 20551264.  edit
  26. ^ a b c Schwartz, S. M.; Daling, J. R.; Doody, D. R.; Wipf, G. C.; Carter, J. J.; Madeleine, M. M.; Mao, E. J.; Fitzgibbons, E. D.; Huang, S.; Beckmann, A. M.; McDougall, J. K.; Galloway, D. A. (1998). "Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection". Journal of the National Cancer Institute 90 (21): 1626–1636. doi:10.1093/jnci/90.21.1626. PMID 9811312.  edit
  27. ^ a b c d Smith, E.; Ritchie, J.; Summersgill, K.; Klussmann, J.; Lee, J.; Wang, D.; Haugen, T.; Turek, L. (Feb 2004). "Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers". International Journal of Cancer. Journal International Du Cancer 108 (5): 766–772. doi:10.1002/ijc.11633. ISSN 0020-7136. PMID 14696105.  edit
  28. ^ a b D'Souza, G.; Kreimer, A.; Viscidi, R.; Pawlita, M.; Fakhry, C.; Koch, W.; Westra, W.; Gillison, M. (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine 356 (19): 1944–1956. doi:10.1056/NEJMoa065497. ISSN 0028-4793. PMID 17494927.  edit
  29. ^ a b Heck, J.; Berthiller, J.; Vaccarella, S.; Winn, D.; Smith, E.; Shan'Gina, O.; Schwartz, S.; Purdue, M.; Pilarska, A.; Eluf-Neto, J.; Menezes, A.; McClean, M. D.; Matos, E.; Koifman, S.; Kelsey, K. T.; Herrero, R.; Hayes, R. B.; Franceschi, S.; Wünsch-Filho, V.; Fernández, L.; Daudt, A. W.; Curado, M. P.; Chen, C.; Castellsagué, X.; Ferro, G.; Brennan, P.; Boffetta, P.; Hashibe, M. (2009). "Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium". International Journal of Epidemiology 39 (1): 166–181. doi:10.1093/ije/dyp350. PMC 2817092. PMID 20022926.  edit
  30. ^ Hemminki, K.; Dong, C.; Frisch, M. (Dec 2000). "Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands". European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 9 (6): 433–437. doi:10.1097/00008469-200012000-00010. ISSN 0959-8278. PMID 11201683.  edit
  31. ^ Tezal, M.; Sullivan Nasca, M.; Stoler, D.; Melendy, T.; Hyland, A.; Smaldino, P.; Rigual, N.; Loree, T. (Apr 2009). "Chronic periodontitis-human papillomavirus synergy in base of tongue cancers". Archives of Otolaryngology—Head & Neck Surgery 135 (4): 391–396. doi:10.1001/archoto.2009.6. ISSN 0886-4470. PMID 19380363.  edit
  32. ^ Tezal, M.; Sullivan, M.; Hyland, A.; Marshall, J.; Stoler, D.; Reid, M.; Loree, T.; Rigual, N.; Merzianu, M.; Hauck, L.; Lillis, C.; Wactawski-Wende, J.; Scannapieco, F. A. (2009). "Chronic periodontitis and the incidence of head and neck squamous cell carcinoma". Cancer Epidemiology, Biomarkers & Prevention 18 (9): 2406–2412. doi:10.1158/1055-9965.EPI-09-0334. PMID 19745222.  edit
  33. ^ Maxwell, J. H.; Kumar, B.; Feng, F. Y.; Worden, F. P.; Lee, J. S.; Eisbruch, A.; Wolf, G. T.; Prince, M. E.; Moyer, J. S.; Teknos, T. N.; Chepeha, D. B.; McHugh, J. B.; Urba, S. G.; Stoerker, J.; Walline, H. M.; Kurnit, D. M.; Cordell, K. G.; Davis, S. J.; Ward, P. D.; Bradford, C. R.; Carey, T. E. (2010). "Tobacco Use in Human Papillomavirus-Positive Advanced Oropharynx Cancer Patients Related to Increased Risk of Distant Metastases and Tumor Recurrence". Clinical Cancer Research 16 (4): 1226–1235. doi:10.1158/1078-0432.CCR-09-2350. PMC 2822887. PMID 20145161.  edit
  34. ^ Kreimer, A.; Bhatia, R.; Messeguer, A.; González, P.; Herrero, R.; Giuliano, A. (2010). "Oral Human Papillomavirus in Healthy Individuals: A Systematic Review of the Literature". Sexually transmitted diseases 37 (6): 386–391. doi:10.1097/OLQ.0b013e3181c94a3b. PMID 20081557.  edit
  35. ^ Lassen, P. (2010). "The role of Human papillomavirus in head and neck cancer and the impact on radiotherapy outcome". Radiotherapy and Oncology 95 (3): 371–380. doi:10.1016/j.radonc.2010.04.022. PMID 20493569.  edit
  36. ^ Eriksen, J. G.; Lassen, P.; Overgaard, J. (2010). "Do all patients with head and neck cancer benefit from radiotherapy and concurrent cetuximab?". The Lancet Oncology 11 (4): 312. doi:10.1016/S1470-2045(10)70035-8. PMID 20359659.  edit
  37. ^ a b Fakhry, C.; Westra, W.; Li, S.; Cmelak, A.; Ridge, J.; Pinto, H.; Forastiere, A.; Gillison, M. (Feb 2008). "Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial" (Free full text). Journal of the National Cancer Institute 100 (4): 261–269. doi:10.1093/jnci/djn011. ISSN 0027-8874. PMID 18270337.  edit
  38. ^ de Jong, M. C.; Pramana, J.; Knegjens, J. L.; Balm, A. J. M.; Van Den Brekel, M. W. M.; Hauptmann, M.; Begg, A. C.; Rasch, C. R. N. (24 March 2010). "HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors". Radiotherapy and Oncology 95 (3): 365–370. doi:10.1016/j.radonc.2010.02.001. ISSN 1879-0887. PMID 20346528.  edit
  39. ^ Ang, K. K.; Harris, J.; Wheeler, R.; Weber, R.; Rosenthal, D. I.; Nguyen-Tân, P. F.; Westra, W. H.; Chung, C. H.; Jordan, R. C.; Lu, C.; Kim, H.; Axelrod, R.; Silverman, C. C.; Redmond, K. P.; Gillison, M. L. (2010). "Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer". New England Journal of Medicine 363 (1): 24–35. doi:10.1056/NEJMoa0912217. PMC 2943767. PMID 20530316.  edit
  40. ^ Lajer, C. B.; Buchwald, C. V. (2010). "The role of human papillomavirus in head and neck cancer". APMIS 118 (6–7): 510. doi:10.1111/j.1600-0463.2010.02624.x. PMID 20553531.  edit
  41. ^ Sturgis, E.; Cinciripini, P. (Oct 2007). "Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers?". Cancer 110 (7): 1429–1435. doi:10.1002/cncr.22963. ISSN 0008-543X. PMID 17724670.  edit
  42. ^ Ernster, J.; Sciotto, C.; O'Brien, M.; Finch, J.; Robinson, L.; Willson, T.; Mathews, M. (Dec 2007). "Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus". The Laryngoscope 117 (12): 2115–2128. doi:10.1097/MLG.0b013e31813e5fbb. ISSN 0023-852X. PMID 17891052.  edit
  43. ^ Hammarstedt, L.; Lindquist, D.; Dahlstrand, H.; Romanitan, M.; Dahlgren, L.; Joneberg, J.; Creson, N.; Lindholm, J.; Ye, W.; Dalianis, T.; Munck-Wikland, E. (Dec 2006). "Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer". International Journal of Cancer. Journal International Du Cancer 119 (11): 2620–2623. doi:10.1002/ijc.22177. ISSN 0020-7136. PMID 16991119.  edit
  44. ^ Chaturvedi, A.; Engels, E.; Anderson, W.; Gillison, M. (Feb 2008). "Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 26 (4): 612–619. doi:10.1200/JCO.2007.14.1713. ISSN 0732-183X. PMID 18235120.  edit
  45. ^ Nguyen, N. P.; Chi, A.; Nguyen, L. M.; Ly, B. H.; Karlsson, U.; Vinh-Hung, V. (2009). "Human papillomavirus-associated oropharyngeal cancer: a new clinical entity". QJM 103 (4): 229–236. doi:10.1093/qjmed/hcp176. PMID 20015950.  edit
  46. ^ Cook, M.; Dawsey, S.; Freedman, N.; Inskip, P.; Wichner, S.; Quraishi, S.; Devesa, S.; McGlynn, K. (2009). "Sex disparities in cancer incidence by time period and age". Cancer Epidemiology, Biomarkers & Prevention 18 (4): 1174–1182. doi:10.1158/1055-9965.EPI-08-1118. PMC 2793271. PMID 19293308.  edit
  47. ^ Chaturvedi, A. K.; Engels, E. A.; Pfeiffer, R. M.; Hernandez, B. Y.; Xiao, W.; Kim, E.; Jiang, B.; Goodman, M. T.; Sibug-Saber, M.; Cozen, W.; Liu, L.; Lynch, C. F.; Wentzensen, N.; Jordan, R. C.; Altekruse, S.; Anderson, W. F.; Rosenberg, P. S.; Gillison, M. L. (2011). "Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States". Journal of Clinical Oncology 29 (32): 4294–4301. doi:10.1200/JCO.2011.36.4596. PMC 3221528. PMID 21969503.  edit
  48. ^ Adelstein, D. J.; Cristina P. Rodriguez (February 3, 2010). "Human Papillomavirus: Changing Paradigms in Oropharyngeal Cancer". Current Oncology Reports (Current Medicine Group LLC) 12 (2): 115–120. doi:10.1007/s11912-010-0084-5. ISSN 1534-6269. PMID 20425596.  edit
  49. ^ a b "Oropharyngeal carcinoma related to human papillomavirus". BMJ 340: c1439. 2010. doi:10.1136/bmj.c1439. ISSN 1468-5833. PMID 20339160.  edit
  50. ^ "Cancer of the Oral Cavity and Pharynx by Subsite". SEER Cancer Statistics Review 1975-2007. Surveillance, Epidemiology and End Results (SEER) Program. 15 April 2010. Retrieved 18 April 2010. 
  51. ^ Näsman, A.; Attner, P.; Hammarstedt, L.; Du, J.; Eriksson, M.; Giraud, G.; Ahrlund-Richter, S.; Marklund, L.; Romanitan, M.; Lindquist, D.; Ramqvist, T. R.; Lindholm, J.; Sparén, P. R.; Ye, W.; Dahlstrand, H.; Munck-Wikland, E.; Dalianis, T. (Jul 2009). "Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?". International Journal of Cancer. Journal International Du Cancer 125 (2): 362–366. doi:10.1002/ijc.24339. ISSN 0020-7136. PMID 19330833.  edit
  52. ^ Hammarstedt, Lalle (2008), Tonsillar Cancer - Incidence, Prevalence of HPV and Survival (PDF), Stockholm, ISBN 978-91-7357-587-4, retrieved 30 April 2010 
  53. ^ Syrjänen, S. (2004). "HPV infections and tonsillar carcinoma". Journal of Clinical Pathology 57 (5): 449–455. doi:10.1136/jcp.2003.008656. PMC 1770289. PMID 15113849.  edit
  54. ^ Tachezy, R. "HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic". Oral Diseases 11 (3): 181–185. doi:10.1111/j.1601-0825.2005.01112.x. ISSN 1354-523X. PMID 15888110.  edit
  55. ^ Hong, A. M.; Grulich, A. E.; Jones, D.; Lee, C. S.; Garland, S. M.; Dobbins, T. A.; Clark, J. R.; Harnett, G. B.; Milross, C. G.; O'Brien, C. J.; Rose, B. R. (2010). "Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets". Vaccine 28 (19): 3269–3272. doi:10.1016/j.vaccine.2010.02.098. PMID 20226244.  edit
  56. ^ Syrjänen, K.; Syrjänen, S.; Lamberg, M.; Pyrhönen, S.; Nuutinen, J. (1983). "Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis". International journal of oral surgery 12 (6): 418–424. doi:10.1016/S0300-9785(83)80033-7. PMID 6325356.  edit
  57. ^ International Agency for Research on Cancer (2007) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. vol 90: Human Papillomaviruses

Further reading[edit]

External links[edit]