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Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 85

Esophageal Squamous Cell Carcinoma, Human Papillomavirus and p16

Department of Pathology, Shridevi Institute of Medical Sciences and Research, Karnataka, India

Date of Web Publication8-Mar-2018

Correspondence Address:
Dr. Mala R Gowda
Department of Pathology, Shridevi Institute of Medical Sciences and Research, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ccij.ccij_7_18

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How to cite this article:
Gowda MR. Esophageal Squamous Cell Carcinoma, Human Papillomavirus and p16. Clin Cancer Investig J 2018;7:85

How to cite this URL:
Gowda MR. Esophageal Squamous Cell Carcinoma, Human Papillomavirus and p16. Clin Cancer Investig J [serial online] 2018 [cited 2020 Jul 9];7:85. Available from:

Dear Editor,

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death.[1] Among the Asian countries, India has a high burden of esophageal cancer.[1] Esophageal cancers are mainly two histopathologicaal types: adenocarcinoma and squamous cell carcinoma.[2] Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype worldwide with high incidence rate in Asia.[2] Esophageal carcinogenesis is a multifactorial process with influence of local environmental conditions, lifestyle, and genetic predisposition.[3] ESCC is usually associated with tobacco and alcohol intake.[1] In northeastern India, where the tobacco and areca nut use is rampant, the incidence of ESCC is relatively high.[1],[2]

Human papillomavirus (HPV) infection as one of the possible etiological factors in ESCC was reported by Syrjänen et al. in 1982.[4] Like HPV-associated head and neck squamous cell carcinoma, HPV-associated ESCCs are associated with favorable prognosis.[1] HPV detection in ESCC is done through polymerase chain reaction, but it is expensive and requires a setup, which may not be available in all the centers. Again, immunohistochemistry for HPV in ESCC gives conflicting results.[1] In such a scenario, p16 expression by immunohistochemistry is usually used as a surrogate marker for HPV infection.[1],[3] The biological rationale underlying this surrogacy stems from the fact that the HPV E7 viral protein triggers degradation of the retinoblastoma tumor suppressor protein in infected cells, which in turn initiates a feedback loop that results increased expression of p16. Immunohistochemical expression of p16 is cost-effective and technically straightforward with high sensitivity.[1]

However, the use of p16 as a surrogate marker of HPV has few disadvantages. As with any surrogate biomarker, there is a risk of discordance between p16 status and the actual HPV status due to failure to use a stringent cutoff for p16-positive tumor cells.[5] Moreover, p16 expression does not discriminate between HPV16 and non-HPV16 subtypes.[5]

Expression of p16 is usually used as surrogate marker for HPV in ESCC and is associated with relatively better outcome.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kumar R, Ghosh SK, Verma AK, Talukdar A, Deka MK, Wagh M, et al. P16 expression as a surrogate marker for HPV infection in esophageal squamous cell carcinoma can predict response to neo-adjuvant chemotherapy. Asian Pac J Cancer Prev 2015;16:7161-5.  Back to cited text no. 1
Dey B, Raphael V, Khonglah Y, GiriLynrah K. Expression of cyclin D1 and P16 in esophageal squamous cell carcinoma. Middle East J Dig Dis 2015;7:220-5.  Back to cited text no. 2
Dey B, Raphael V, Khonglah Y, Lynrah KG. Molecular alterations and targeted therapy in oesophageal squamous cell carcinoma. Int Res J Pharm 2012;3:15-8.  Back to cited text no. 3
Syrjänen K, Pyrhönen S, Aukee S, Koskela E. Squamous cell papilloma of the esophagus: A tumour probably caused by human papilloma virus (HPV). Diagn Histopathol 1982;5:291-6.  Back to cited text no. 4
Bonner JA, Mesia R, Giralt J, Psyrri A, Keilholz U, Rosenthal DI, et al. P16, HPV, and cetuximab: What is the evidence? Oncologist 2017;22:811-22.  Back to cited text no. 5


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