Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance
Year 2018,
Volume: 8 Issue: 1, 13 - 18, 05.04.2018
Objective: The rise in the number of cancer
cases with human papilloma virus (HPV)-positive squamous carcinoma of
the oropharynx makes the detection of HPV clinically important. We aimed
to investigate the HPV positivity in our patients who have
oropharyngeal cancer and compare the two different HPV detection
methods, which are HPV in situ hybridization (ISH) and p16
immunohistochemistry (IHC), and show the staining patterns.
Methods:
Twenty-three specimens of oropharyngeal cancer patients and ten
tonsillectomy specimens that revealed no cancerous tissue (control
group) were collected from retrospective file analysis. All specimens
were evaluated by both p16 IHC and HPV ISH on paraffin blocks.
Results:
Seven of 23 cases showed p16 expression. Of all these 7 cases that
showed p16 expression, six showed high p16 expression and one showed low
p16 expression. All six cases that showed high p16 expression were HPV
ISH (+). One case that showed low expression of p16 was HPV ISH (-). All
cases that were p16 (+) showed diffuse p16 expression and none of the
cases showed focal p16 expression.
Conclusion: High
p16 expression (>70%) is a reliable marker of HPV positivity.
Combining p16 IHC with HPV ISH will further improve its specificity. All
p16 positive cases showed diffuse p16 expression, thus did not show
tumor heterogeneity, suggesting that even a biopsy specimen showing
diffuse p16 expression shows p16 positivity of the whole tumoral tissue.
1. Cerezo L, de la Torre A, Hervas A, et al. Oropharyngeal cancer
related to Human Papilloma Virus: incidence and prognosis in
Madrid, Spain. Clin Transl Oncol 2014;16:301–6.
2. Duray A, Descamps G, Decaestecker C, et al. Human papillo-
mavirus DNA strongly correlates with a poorer prognosis in oral
cavity carcinoma. Laryngoscope 2012;122:1558–65.
3. Zaravinos A. An updated overview of HPV-associated head and
neck carcinomas. Oncotarget 2014;5:3956–69.
4. Gillison ML, Shah KV. Human papillomavirus-associated head
and neck squamous cell carcinoma: mounting evidence for an eti-
ologic role for human papillomavirus in a subset of head and neck
cancers. Curr Opin Oncol 2001;13:183–8.
5. Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associat-
ed head and neck cancer: a virus-related cancer epidemic. Lancet
Oncol 2010;11:781–9.
6. Schache AG, Liloglou T, Risk JM, Filia A, Jones TM, Sheard J, et
al. Evaluation of human papilloma virus diagnostic testing in
oropharyngeal squamous cell carcinoma: sensitivity, specificity,
and prognostic discrimination. Clin Cancer Res 2011;17:6262–71.
7. Conway DI, Stockton DL, Warnakulasuriya KA, Ogden G,
Macpherson LM. Incidence of oral and oropharyngeal cancer in
United Kingdom (1990–1999) – recent trends and regional varia-
tion. Oral Oncol 2006;42:586–92.
8. Rampias TN, Fragoulis EG, Sideris DC. Efficient cloning of alter-
natively polyadenylated transcripts via hybridization capture PCR.
Curr Issues Mol Biol 2012;14:1–8.
9. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and
survival of patients with oropharyngeal cancer. N Engl J Med
2010;363:24–35.
10. Fakhry C, Gillison ML. Clinical implications of human papillo-
mavirus in head and neck cancers. J Clin Oncol 2006;24:2606–11.
11. Lewis JS, Thorstad WL, Chernock RD, et al. p16 Positive oropha-
ryngeal squamous cell carcinoma: an entity with a favorable prog-
nosis regardless of tumor hpv status. Am J Surg Pathol 2010;
34:1088–96.
12. Näsman A, Attner P, Hammarstedt L, et al. Incidence of human
papillomavirus (HPV) positive tonsillar carcinoma in Stockholm,
Sweden: an epidemic of viral-induced carcinoma? Int J Cancer
2009;125:362–6.
13. Tural D, Elicin O, Batur S, et al. Increase in the rate of HPV pos-
itive oropharyngeal cancers during 1996-2011 in a case study in
Turkey. Asian Pac J Cancer Prev 2013;14:6065–8.
14. Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropha-
ryngeal squamous cell carcinoma using human papillomavirus test-
ing. Oral Oncol 2010;46:492–6.
15. Braakhuis BJ, Brakenhoff RH, Meijer CJ, Snijders PJ, Leemans
CR. Human papilloma virus in head and neck cancer: the need for
a standardised assay to assess the full clinical importance. Eur J
Cancer 2009;45:2935–9.
16. Kim TW, Choi SY, Ko YH, Baek CH, Son YI. The prognostic
role of p16 expression in tonsil cancer treated by either surgery or
radiation. Clin Exp Otorhinolaryngol 2012;5:207–12.
17. Thomas J, Primeaux T. Is p16 immunohistochemistry a more
cost-effective method for identification of human papilloma virus-
associated head and neck squamous cell carcinoma? Ann Diagn
Pathol 2012;16:91–9.
18. El-Naggar AK, Westra WH. p16 expression as a surrogate mark-
er for HPV-related oropharyngeal carcinoma: a guide for interpre-
tative relevance and consistency. Head Neck 2012;34:459–61.
19. Schlecht NF, Brandwein-Gensler M, Nuovo GJ, et al. A compar-
ison of clinically utilized human papillomavirus detection methods
in head and neck cancer. Mod Pathol 2011;24:1295–305.
20. Thavaraj S, Stokes A, Guerra E, et al. Evaluation of human papil-
lomavirus testing for squamous cell carcinoma of the tonsil in clin-
ical practice. J Clin Pathol 2011;64:308–12.
21. Bussu F, Sali M, Gallus R, Vellone VG, Zannoni GF, Autorino R, et
al. HPV infection in squamous cell carcinomas arising from different
mucosal sites of the head and neck region. Is p16 immunohistochem-
istry a reliable surrogate marker? Br J Cancer 2013;108:1157–62.
22. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W,
Kim E, et al. Human papillomavirus and rising oropharyngeal can-
cer incidence in the United States. J Clin Oncol 2011;29:4294–
301.
23. Sturgis EM, Ang KK. The epidemic of HPV-associated oropha-
ryngeal cancer is here: is it time to change our treatment para-
digms? J Natl Compr Canc Netw 2011;9:665–73.
24. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch
WM, et al. Case-control study of human papillomavirus and
oropharyngeal cancer. N Engl J Med 2007;356:1944–56.
25. Smith EM, Ritchie JM, Summersgill KF, et al. Age, sexual behav-
ior and human papillomavirus infection in oral cavity and oropha-
ryngeal cancers. Int J Cancer 2004;108:766–72.
26. Dagogo-Jack I, Shaw A. Tumour heterogeneity and resistance to
cancer therapies. Nat Rev Clin Oncol 2018;15(2):81–94.
Year 2018,
Volume: 8 Issue: 1, 13 - 18, 05.04.2018
1. Cerezo L, de la Torre A, Hervas A, et al. Oropharyngeal cancer
related to Human Papilloma Virus: incidence and prognosis in
Madrid, Spain. Clin Transl Oncol 2014;16:301–6.
2. Duray A, Descamps G, Decaestecker C, et al. Human papillo-
mavirus DNA strongly correlates with a poorer prognosis in oral
cavity carcinoma. Laryngoscope 2012;122:1558–65.
3. Zaravinos A. An updated overview of HPV-associated head and
neck carcinomas. Oncotarget 2014;5:3956–69.
4. Gillison ML, Shah KV. Human papillomavirus-associated head
and neck squamous cell carcinoma: mounting evidence for an eti-
ologic role for human papillomavirus in a subset of head and neck
cancers. Curr Opin Oncol 2001;13:183–8.
5. Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associat-
ed head and neck cancer: a virus-related cancer epidemic. Lancet
Oncol 2010;11:781–9.
6. Schache AG, Liloglou T, Risk JM, Filia A, Jones TM, Sheard J, et
al. Evaluation of human papilloma virus diagnostic testing in
oropharyngeal squamous cell carcinoma: sensitivity, specificity,
and prognostic discrimination. Clin Cancer Res 2011;17:6262–71.
7. Conway DI, Stockton DL, Warnakulasuriya KA, Ogden G,
Macpherson LM. Incidence of oral and oropharyngeal cancer in
United Kingdom (1990–1999) – recent trends and regional varia-
tion. Oral Oncol 2006;42:586–92.
8. Rampias TN, Fragoulis EG, Sideris DC. Efficient cloning of alter-
natively polyadenylated transcripts via hybridization capture PCR.
Curr Issues Mol Biol 2012;14:1–8.
9. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and
survival of patients with oropharyngeal cancer. N Engl J Med
2010;363:24–35.
10. Fakhry C, Gillison ML. Clinical implications of human papillo-
mavirus in head and neck cancers. J Clin Oncol 2006;24:2606–11.
11. Lewis JS, Thorstad WL, Chernock RD, et al. p16 Positive oropha-
ryngeal squamous cell carcinoma: an entity with a favorable prog-
nosis regardless of tumor hpv status. Am J Surg Pathol 2010;
34:1088–96.
12. Näsman A, Attner P, Hammarstedt L, et al. Incidence of human
papillomavirus (HPV) positive tonsillar carcinoma in Stockholm,
Sweden: an epidemic of viral-induced carcinoma? Int J Cancer
2009;125:362–6.
13. Tural D, Elicin O, Batur S, et al. Increase in the rate of HPV pos-
itive oropharyngeal cancers during 1996-2011 in a case study in
Turkey. Asian Pac J Cancer Prev 2013;14:6065–8.
14. Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropha-
ryngeal squamous cell carcinoma using human papillomavirus test-
ing. Oral Oncol 2010;46:492–6.
15. Braakhuis BJ, Brakenhoff RH, Meijer CJ, Snijders PJ, Leemans
CR. Human papilloma virus in head and neck cancer: the need for
a standardised assay to assess the full clinical importance. Eur J
Cancer 2009;45:2935–9.
16. Kim TW, Choi SY, Ko YH, Baek CH, Son YI. The prognostic
role of p16 expression in tonsil cancer treated by either surgery or
radiation. Clin Exp Otorhinolaryngol 2012;5:207–12.
17. Thomas J, Primeaux T. Is p16 immunohistochemistry a more
cost-effective method for identification of human papilloma virus-
associated head and neck squamous cell carcinoma? Ann Diagn
Pathol 2012;16:91–9.
18. El-Naggar AK, Westra WH. p16 expression as a surrogate mark-
er for HPV-related oropharyngeal carcinoma: a guide for interpre-
tative relevance and consistency. Head Neck 2012;34:459–61.
19. Schlecht NF, Brandwein-Gensler M, Nuovo GJ, et al. A compar-
ison of clinically utilized human papillomavirus detection methods
in head and neck cancer. Mod Pathol 2011;24:1295–305.
20. Thavaraj S, Stokes A, Guerra E, et al. Evaluation of human papil-
lomavirus testing for squamous cell carcinoma of the tonsil in clin-
ical practice. J Clin Pathol 2011;64:308–12.
21. Bussu F, Sali M, Gallus R, Vellone VG, Zannoni GF, Autorino R, et
al. HPV infection in squamous cell carcinomas arising from different
mucosal sites of the head and neck region. Is p16 immunohistochem-
istry a reliable surrogate marker? Br J Cancer 2013;108:1157–62.
22. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W,
Kim E, et al. Human papillomavirus and rising oropharyngeal can-
cer incidence in the United States. J Clin Oncol 2011;29:4294–
301.
23. Sturgis EM, Ang KK. The epidemic of HPV-associated oropha-
ryngeal cancer is here: is it time to change our treatment para-
digms? J Natl Compr Canc Netw 2011;9:665–73.
24. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch
WM, et al. Case-control study of human papillomavirus and
oropharyngeal cancer. N Engl J Med 2007;356:1944–56.
25. Smith EM, Ritchie JM, Summersgill KF, et al. Age, sexual behav-
ior and human papillomavirus infection in oral cavity and oropha-
ryngeal cancers. Int J Cancer 2004;108:766–72.
26. Dagogo-Jack I, Shaw A. Tumour heterogeneity and resistance to
cancer therapies. Nat Rev Clin Oncol 2018;15(2):81–94.
Önerci Çelebi, Ö., Şener, E., Çisel Aydın, M., Tezel, G. G. (2018). Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance. ENT Updates, 8(1), 13-18.
AMA
Önerci Çelebi Ö, Şener E, Çisel Aydın M, Tezel GG. Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance. ENT Updates. April 2018;8(1):13-18.
Chicago
Önerci Çelebi, Özlem, Ebru Şener, Makbule Çisel Aydın, and Gaye Güler Tezel. “Detection of Human Papilloma Virus in Normal and Tumoral Oropharyngeal Tissue Using HPV DNA in Situ Hybridization and p16 Expression and Its Clinicopathologic Importance”. ENT Updates 8, no. 1 (April 2018): 13-18.
EndNote
Önerci Çelebi Ö, Şener E, Çisel Aydın M, Tezel GG (April 1, 2018) Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance. ENT Updates 8 1 13–18.
IEEE
Ö. Önerci Çelebi, E. Şener, M. Çisel Aydın, and G. G. Tezel, “Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance”, ENT Updates, vol. 8, no. 1, pp. 13–18, 2018.
ISNAD
Önerci Çelebi, Özlem et al. “Detection of Human Papilloma Virus in Normal and Tumoral Oropharyngeal Tissue Using HPV DNA in Situ Hybridization and p16 Expression and Its Clinicopathologic Importance”. ENT Updates 8/1 (April 2018), 13-18.
JAMA
Önerci Çelebi Ö, Şener E, Çisel Aydın M, Tezel GG. Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance. ENT Updates. 2018;8:13–18.
MLA
Önerci Çelebi, Özlem et al. “Detection of Human Papilloma Virus in Normal and Tumoral Oropharyngeal Tissue Using HPV DNA in Situ Hybridization and p16 Expression and Its Clinicopathologic Importance”. ENT Updates, vol. 8, no. 1, 2018, pp. 13-18.
Vancouver
Önerci Çelebi Ö, Şener E, Çisel Aydın M, Tezel GG. Detection of human papilloma virus in normal and tumoral oropharyngeal tissue using HPV DNA in situ hybridization and p16 expression and its clinicopathologic importance. ENT Updates. 2018;8(1):13-8.