Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer (Review)

Sivars,Lars; Bersani,Cinzia; Grün,Nathalie; Ramqvist,Torbjörn; Munck‑Wikland,Eva; von Buchwald,Christian; Dalianis,Tina

doi:10.3892/mco.2016.1050

Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer (Review)

Authors:
- Lars Sivars
- Cinzia Bersani
- Nathalie Grün
- Torbjörn Ramqvist
- Eva Munck‑Wikland
- Christian von Buchwald
- Tina Dalianis
View Affiliations

Affiliations: Department of Oncology‑Pathology, Karolinska Institutet, Stockholm, Sweden, Department of Clinical, Technical Sciences and Intervention, Karolinska Institutet, Stockholm, Sweden, Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Published online on: October 13, 2016 https://doi.org/10.3892/mco.2016.1050
Pages: 671-674

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squamous cell carcinoma (OPSCC), particularly of the tonsils and base of the tongue (TSCC and BOTSCC, respectively). Moreover, HPV‑positive TSCC and BOTSCC are associated with a better outcome compared with their HPV‑negative counterparts (80 vs. 40% 3‑year disease‑free survival rate, respectively) and their incidence has increased in several countries. Recently, accumulating evidence of HPV in a considerable proportion of cancers of unknown primary (CUP) in the head and neck region and in a small proportion of hypopharyngeal SCCs has been reported. Furthermore, HPV‑positive tumours, particularly cases with HPV DNA positivity in combination with overexpression of p16, also tend to have a better clinical outcome compared with that of the corresponding HPV‑negative tumours. This finding is particularly prominent in HPV‑positive CUPs of the head and neck region, where the primary tumour likely originates from the oropharynx. Thus, the determination of HPV status and p16 expression may be of value for the diagnosis and treatment of CUP of the head and neck region and may also be of value for hypopharyngeal cancers in the future. However, for hypopharyngeal cancer as well as other non‑OPSCCs, additional studies per subsite on the effect of HPV status on survival are required.

View Figures

View References

1	Dalianis T: Human papillomavirus and oropharyngeal cancer, the epidemics, and significance of additional clinical biomarkers for prediction of response to therapy (Review). Int J Oncol. 44:1799–1805. 2014.PubMed/NCBI
2	Marklund L, Näsman A, Ramqvist T, Dalianis T, Munck-Wikland E and Hammarstedt L: Prevalence of human papillomavirus and survival in oropharyngeal cancer other than tonsil or base of tongue cancer. Cancer Med. 1:82–88. 2012. View Article : Google Scholar : PubMed/NCBI
3	Lindquist D, Romanitan M, Hammarstedt L, Näsman A, Dahlstrand H, Lindholm J, Onelöv L, Ramqvist T, Ye W, Munck-Wikland E and Dalianis T: Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol. 1:350–335. 2007. View Article : Google Scholar : PubMed/NCBI
4	Attner P, Du J, Näsman A, Hammarstedt L, Ramqvist T, Lindholm J, Marklund L, Dalianis T and Munck-Wikland E: Human papillomavirus and survival in patients with base of tongue cancer. Int J Cancer. 128:2892–2897. 2011. View Article : Google Scholar : PubMed/NCBI
5	Sturgis EM and Cinciripini PM: Trends in head and neck cancer incidence in relation to smoking prevalence: An emerging epidemic of human papillomavirus-associated cancers? Cancer. 110:1429–1435. 2007. View Article : Google Scholar : PubMed/NCBI
6	Näsman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, et al: Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral-induced carcinoma? Int J Cancer. 125:362–366. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, et al: Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 29:4294–4301. 2011. View Article : Google Scholar : PubMed/NCBI
8	Channir HI, Rubek N, Nielsen HU, Kiss K, Charabi BW, Lajer CB and von Buchwald C: Transoral robotic surgery for the management of head and neck squamous cell carcinoma of unknown primary. Acta Otolaryngol. 135:1051–1057. 2015. View Article : Google Scholar : PubMed/NCBI
9	Tertipis N, Hammar U, Näsman A, Vlastos A, Nordfors C, Grün N, Ährlund-Richter A, Sivars L, Haeggblom L, Marklund L, et al: A model for predicting clinical outcome in patients with human papillomavirus-positive tonsillar and base of tongue cancer. Eur J Cancer. 51:1580–1587. 2015. View Article : Google Scholar : PubMed/NCBI
10	Begum S, Gillison ML, Nicol TL and Westra WH: Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 13:1186–1191. 2007. View Article : Google Scholar : PubMed/NCBI
11	Compton AM, Moore-Medlin T, Herman-Ferdinandez L, Clark C, Caldito GC, Wang XI, Thomas J, Abreo FW and Nathan CO: Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 145:51–57. 2011. View Article : Google Scholar : PubMed/NCBI
12	Tribius S, Hoffmann AS, Bastrop S, Görögh T, Haag J, Röcken C, Clauditz T, Grob T, Wilczak W, Tennstedt P, et al: HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome. Oral Oncol. 48:1178–1184. 2012. View Article : Google Scholar : PubMed/NCBI
13	Park GC, Lee M, Roh JL, Yu MS, Choi SH, Nam SY, Kim SY and Cho KJ: Human papillomavirus and p16 detection in cervical lymph node metastases from an unknown primary tumor. Oral Oncol. 48:1250–1256. 2012. View Article : Google Scholar : PubMed/NCBI
14	Sivars L, Näsman A, Tertipis N, Vlastos A, Ramqvist T, Dalianis T, Munck-Wikland E and Nordemar S: Human papillomavirus and p53 expression in cancer of unknown primary in the head and neck region in relation to clinical outcome. Cancer Med. 3:376–384. 2014. View Article : Google Scholar : PubMed/NCBI
15	Jensen DH, Hedback N, Specht L, Høgdall E, Andersen E, Therkildsen MH, Friis-Hansen L, Norrild B and von Buchwald C: Human papillomavirus in head and neck squamous cell carcinoma of unknown primary is a common event and a strong predictor of survival. PLoS One. 9:e1104562014. View Article : Google Scholar : PubMed/NCBI
16	Davis KS, Byrd JK, Mehta V, Chiosea SI, Kim S, Ferris RL, Johnson JT and Duvvuri U: Occult primary head and neck squamous cell carcinoma: Utility of discovering primary lesions. Otolaryngol Head Neck Surg. 151:272–278. 2014. View Article : Google Scholar : PubMed/NCBI
17	Boscolo-Rizzo P, Schroeder L, Romeo S and Pawlita M: The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: A systematic review. Clin Exp Metastasis. 32:835–845. 2015. View Article : Google Scholar : PubMed/NCBI
18	Hoffmann M, Görögh T, Gottschlich S, Lohrey C, Rittgen W, Ambrosch P, Schwarz E and Kahn T: Human papillomaviruses in head and neck cancer: 8 year-survival-analysis of 73 patients. Cancer Lett. 218:199–206. 2005. View Article : Google Scholar : PubMed/NCBI
19	Ernoux-Neufcoeur P, Arafa M, Decaestecker C, Duray A, Remmelink M, Leroy X, Herfs M, Somja J, Depuydt CE, Delvenne P and Saussez S: Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma. J Cancer Res Clin Oncol. 137:173–181. 2011. View Article : Google Scholar : PubMed/NCBI
20	Wendt M, Romanitan M, Näsman A, Dalianis T, Hammarstedt L, Marklund L, Ramqvist T and Munck-Wikland E: Presence of human papillomaviruses and p16 expression in hypopharyngeal cancer. Head Neck. 36:107–112. 2014. View Article : Google Scholar : PubMed/NCBI
21	Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsagué X, Laporte L, Bosch FX, de Sanjosé S and Trottier H: HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: A systematic review and meta-analysis. Lancet Oncol. 15:1319–1331. 2014. View Article : Google Scholar : PubMed/NCBI
22	Dalianis T, Grün N, Koch J, Vlastos A, Tertipis N, Nordfors C, Näsman A, Wendt M, Romanitan M, Bersani C, et al: Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden. Oral Oncol. 51:857–861. 2015. View Article : Google Scholar : PubMed/NCBI
23	Rodrigo JP, Hermsen MA, Fresno MF, Brakenhoff RH, García-Velasco F, Snijders PJ, Heideman DA and García-Pedrero JM: Prevalence of human papillomavirus in laryngeal and hypopharyngeal squamous cell carcinomas in northern Spain. Cancer Epidemiol. 39:37–41. 2015. View Article : Google Scholar : PubMed/NCBI
24	Joo YH, Lee YS, Cho KJ, Park JO, Nam IC, Kim CS, Kim SY and Kim MS: Characteristics and prognostic implications of high-risk HPV-associated hypopharyngeal cancers. PLoS One. 8:e787182013. View Article : Google Scholar : PubMed/NCBI
25	Wilson DD, Rahimi AS, Saylor DK, Stelow EB, Jameson MJ, Shonka DC, Reibel JF, Levine PA and Read PW: p16 not a prognostic marker for hypopharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 138:556–561. 2012. View Article : Google Scholar : PubMed/NCBI
26	Castellsagué X, Alemany L, Quer M, Halec G, Quirós B, Tous S, Clavero O, Alòs L, Biegner T, Szafarowski T, et al: HPV Involvement in head and neck cancers: Comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst. 108:djv4032016. View Article : Google Scholar : PubMed/NCBI
27	Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM, Wang D, Redmond KP, Shenouda G, Trotti A, et al: p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clini Oncol. 32:3930–3938. 2014. View Article : Google Scholar
28	Shaughnessy JN, Farghaly H, Wilson L, Redman R, Potts K, Bumpous J, Silverman C and Dunlap NE: HPV: A factor in organ preservation for locally advanced larynx and hypopharynx cancer? Am J Otolaryngol. 35:19–24. 2014. View Article : Google Scholar : PubMed/NCBI
29	Young RJ, Urban D, Angel C, Corry J, Lyons B, Vallance N, Keid S, Iseli TA, Solomon B and Rischin D: Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma. Br J Cancer. 112:1098–1104. 2015. View Article : Google Scholar : PubMed/NCBI