1887

Abstract

Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74 % of the HPV-positive cases. HPV was detected in 65 % (92/141) and 11 % (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (<0.0001). HPV was detected in 73 % (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell (range 0.003–1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100 % (17/17) and 68 % (40/58) for those with <1 HPV16 copy cell and >1 HPV16 copy cell, respectively (=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6 %, whereas entirely episomal and mixed virus was detected in 51 and 42 % of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48 %), the episomal HPV16 is salient (93 %) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.

Keyword(s): HNSCC and HPV
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000611
2016-11-10
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/11/2949.html?itemId=/content/journal/jgv/10.1099/jgv.0.000611&mimeType=html&fmt=ahah

References

  1. Arbyn M., Tommasino M., Depuydt C., Dillner J. 2014; Are 20 human papillomavirus types causing cervical cancer?. J Pathol 234:431–435 [View Article][PubMed]
    [Google Scholar]
  2. Arias-Pulido H., Peyton C. L., Joste N. E., Vargas H., Wheeler C. M. 2006; Human papillomavirus type 16 integration in cervical carcinoma in situ and in invasive cervical cancer. J Clin Microbiol 44:1755–1762 [View Article][PubMed]
    [Google Scholar]
  3. Badaracco G., Venuti A., Morello R., Muller A., Marcante M. L. 2000; Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. Anticancer Res 20:1301–1305[PubMed]
    [Google Scholar]
  4. Badaracco G., Venuti A., Sedati A., Marcante M. L. 2002; HPV16 and HPV18 in genital tumors: significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol 67:574–582 [View Article][PubMed]
    [Google Scholar]
  5. Badaracco G., Rizzo C., Mafera B., Pichi B., Giannarelli D., Rahimi S. S., Vigili M. G., Venuti A. 2007; Molecular analyses and prognostic relevance of HPV in head and neck tumours. Oncol Rep 17:931–939 [View Article][PubMed]
    [Google Scholar]
  6. Cohen M. A., Basha S. R., Reichenbach D. K., Robertson E., Sewell D. A. 2008; Increased viral load correlates with improved survival in HPV-16-associated tonsil carcinoma patients. Acta Otolaryngol 128:583–589 [View Article][PubMed]
    [Google Scholar]
  7. Collins S. I., Constandinou-Williams C., Wen K., Young L. S., Roberts S., Murray P. G., Woodman C. B. 2009; Disruption of the E2 gene is a common and early event in the natural history of cervical human papillomavirus infection: a longitudinal cohort study. Cancer Res 69:3828–3832 [View Article][PubMed]
    [Google Scholar]
  8. Das B. C., Sharma J. K., Gopalakrishna V., Luthra U. K. 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 [View Article][PubMed]
    [Google Scholar]
  9. Deng Z., Hasegawa M., Kiyuna A., Matayoshi S., Uehara T., Agena S., Yamashita Y., Ogawa K., Maeda H., Suzuki M. 2013; Viral load, physical status, and E6/E7 mRNA expression of human papillomavirus in head and neck squamous cell carcinoma. Head Neck 35:800–808 [View Article][PubMed]
    [Google Scholar]
  10. Doeberitz M., Vinokurova S. 2009; Host factors in HPV-related carcinogenesis: cellular mechanisms controlling HPV infections. Arch Med Res 40:435–442 [View Article][PubMed]
    [Google Scholar]
  11. Gillison M. L., Chaturvedi A. K., Anderson W. F., Fakhry C. 2015; Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol 33:3235–3242 [View Article][PubMed]
    [Google Scholar]
  12. Guo M., Sneige N., Silva E. G., Jan Y. J., Cogdell D. E., Lin E., Luthra R., Zhang W. 2007; Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma. Mod Pathol 20:256–266 [View Article][PubMed]
    [Google Scholar]
  13. Hansson B. G., Rosenquist K., Antonsson A., Wennerberg J., Schildt E. B., Bladström A., Andersson G. 2005; Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta Otolaryngol 125:1337–1344 [View Article][PubMed]
    [Google Scholar]
  14. Ho C. M., Chien T. Y., Huang S. H., Lee B. H., Chang S. F. 2006; Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer. Gynecol Oncol 102:54–60 [View Article][PubMed]
    [Google Scholar]
  15. Holzinger D., Schmitt M., Dyckhoff G., Benner A., Pawlita M., Bosch F. X. 2012; Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res 72:4993–5003 [View Article][PubMed]
    [Google Scholar]
  16. Klussmann J. P., Weissenborn S. J., Wieland U., Dries V., Kolligs J., Jungehuelsing M., Eckel H. E., Dienes H. P., Pfister H. J., Fuchs P. G. 2001; Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 92:2875–2884 [View Article][PubMed]
    [Google Scholar]
  17. Koskinen W. J., Chen R. W., Leivo I., Mäkitie A., Bäck L., Kontio R., Suuronen R., Lindqvist C., Auvinen E. et al. 2003; Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int J Cancer 107:401–406 [View Article][PubMed]
    [Google Scholar]
  18. Kreimer A. R., Clifford G. M., Boyle P., Franceschi S. 2005; Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14:467–475 [View Article][PubMed]
    [Google Scholar]
  19. Kristiansen E., Jenkins A., Holm R. 1994; Coexistence of episomal and integrated HPV16 DNA in squamous cell carcinoma of the cervix. J Clin Pathol 47:253–256 [View Article][PubMed]
    [Google Scholar]
  20. Letsolo B. T., Faust H., Ekblad L., Wennerberg J., Forslund O. 2016; Establishment and characterization of a human papillomavirus type 16-positive tonsillar carcinoma xenograft in BALB/c nude mice. Head Neck 38:417–425 [View Article][PubMed]
    [Google Scholar]
  21. Matsukura T., Koi S., Sugase M. 1989; Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology 172:63–72 [View Article][PubMed]
    [Google Scholar]
  22. Mellin H., Dahlgren L., Munck-Wikland E., Lindholm J., Rabbani H., Kalantari M., Dalianis T. 2002; Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer 102:152–158 [View Article][PubMed]
    [Google Scholar]
  23. Näsman A., Nordfors C., Holzhauser S., Vlastos A., Tertipis N., Hammar U., Hammarstedt-Nordenvall L., Marklund L., Munck-Wikland E. et al. 2015; Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma?. Eur J Cancer 51:55–61 [View Article][PubMed]
    [Google Scholar]
  24. Parfenov M., Pedamallu C. S., Gehlenborg N., Freeman S. S., Danilova L., Bristow C. A., Lee S., Hadjipanayis A. G., Ivanova E. V. et al. 2014; Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci U S A 111:15544–15549 [View Article][PubMed]
    [Google Scholar]
  25. Park J. S., Hwang E. S., Park S. N., Ahn H. K., Um S. J., Kim C. J., Kim S. J., Namkoong S. E. 1997; Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol 65:121–129 [View Article][PubMed]
    [Google Scholar]
  26. Peitsaro P., Johansson B., Syrjänen S. 2002; Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique. J Clin Microbiol 40:886–891 [View Article][PubMed]
    [Google Scholar]
  27. Reuschenbach M., Huebbers C. U., Prigge E. S., Bermejo J. L., Kalteis M. S., Preuss S. F., Seuthe I. M., Kolligs J., Speel E. J. et al. 2015; Methylation status of HPV16 E2-binding sites classifies subtypes of HPV-associated oropharyngeal cancers. Cancer 121:1966–1976 [View Article][PubMed]
    [Google Scholar]
  28. Ruutu M. P., Kulmala S. M., Peitsaro P., Syrjänen S. M. 2008; The performance of the HPV16 real-time PCR integration assay. Clin Biochem 41:423–428 [View Article][PubMed]
    [Google Scholar]
  29. Saulle R., Semyonov L., Mannocci A., Careri A., Saburri F., Ottolenghi L., Guerra F., La Torre G. 2015; Human papillomavirus and cancerous diseases of the head and neck: a systematic review and meta-analysis. Oral Dis 21:417–431 [View Article][PubMed]
    [Google Scholar]
  30. Schmitt M., Bravo I. G., Snijders P. J., Gissmann L., Pawlita M., Waterboer T. 2006; Bead-based multiplex genotyping of human papillomaviruses. J Clin Microbiol 44:504–512 [View Article][PubMed]
    [Google Scholar]
  31. Snow A. N., Laudadio J. 2010; Human papillomavirus detection in head and neck squamous cell carcinomas. Adv Anat Pathol 17:394–403 [View Article][PubMed]
    [Google Scholar]
  32. Söderlund-Strand A., Carlson J., Dillner J. 2009; Modified general primer PCR system for sensitive detection of multiple types of oncogenic human papillomavirus. J Clin Microbiol 47:541–546 [View Article][PubMed]
    [Google Scholar]
  33. Stein A. P., Saha S., Kraninger J. L., Swick A. D., Yu M., Lambert P. F., Kimple R. J. 2015; Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. Cancer J 21:138–146 [CrossRef]
    [Google Scholar]
  34. Sturegård E., Johansson H., Ekström J., Hansson B. G., Johnsson A., Gustafsson E., Dillner J., Forslund O. 2013; Human papillomavirus typing in reporting of condyloma. Sex Transm Dis 40:123–129 [View Article][PubMed]
    [Google Scholar]
  35. Syrjänen S. 2004; HPV infections and tonsillar carcinoma. J Clin Pathol 57:449–455 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000611
Loading
/content/journal/jgv/10.1099/jgv.0.000611
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error