p16 Expression as a Surrogate Marker for HPV Infection in Esophageal Squamous Cell Carcinoma can Predict Response to Neo-Adjuvant Chemotherapy

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer. Currently, human papillomavirus (HPV) is considered as a potential risk factor for ESCC, but this assumption is still contradictory. PI3K/Akt/mTOR network plays a key role in the virus/host cell crosstalk in HPV positive cancer cells. The purpose of this study was to investigate the relationship between the expression of PIK3CA, PIK3CB and HPV infection. Methods: The expression of PIK3CA, PIK3CB, p16 and p53 in 156 cases of ESCC was detected by immunohistochemistry. Patients are followed up by telephone or clinic. Results: In this study, the positive rates of PIK3CA, PIK3CB, p53 and p16 in ESCC were significantly higher than in normal esophageal mucosa. The expression of PIK3CA and PIK3CB was related to TNM stage and lymph node metastasis. The expression of p53 is related to the depth of tumor invasion. High p16 expression was found to be significantly correlated with tumor location, TNM stage, differentiation grade and lymph node metastasis. P16 expression is positively correlated with PIK3CA expression but not with PIK3CB and p53. Survival analysis further indicated that that PIK3CA and p53 were markers of poor diagnosis. P16 is a mark of favorable prognosis in ESCC. Conclusions: The expression of PIK3CA and PIK3CB is related to the development of ESCC. The imbalance of PI3K/Akt signaling pathway is closely related to HPV infection and prognosis. The combined detection of PIK3CA and p16 is of great significance to evaluate the prognosis and optimize the treatment of ESCC.

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Prognostic role of HPV infection in esophageal squamous cell carcinoma

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2018.10.304 ◽

2019 ◽

Vol 45 (2) ◽

pp. e85

Author(s):

L. Bognar ◽

S. Bellyei ◽

I. Hegedus ◽

K. Gombos ◽

O.P. Horvath ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Prognostic Role

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HPV infection in Brazilian patients with esophageal squamous cell carcinoma: Interpopulational differences, lack of correlation with surrogate markers and clinicopathological parameters

Cancer Letters ◽

10.1016/j.canlet.2012.07.018 ◽

2012 ◽

Vol 326 (1) ◽

pp. 52-58 ◽

Cited By ~ 19

Author(s):

Suellen Herbster ◽

Cintia Tereza Lima Ferraro ◽

Natália Kirsch Koff ◽

Ana Rossini ◽

Cleber Dario Pinto Kruel ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Clinicopathological Parameters ◽

Surrogate Markers ◽

Interpopulational Differences

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Prognostic role of HPV infection in esophageal squamous cell carcinoma

Infectious Agents and Cancer ◽

10.1186/s13027-018-0210-9 ◽

2018 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Laura Bognár ◽

Ivett Hegedűs ◽

Szabolcs Bellyei ◽

Éva Pozsgai ◽

László Zoltán ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Prognostic Role

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Pharmacokinetic study of Neo-Adjuvant chemotherapy combining Carboplatin, Cisplatin and 5-Fluorouracil in head and neck squamous cell carcinoma

Proceedings of the 3rd International Congress on Neo-Adjuvant Chemotherapy ◽

10.1007/978-2-8178-0782-9_94 ◽

1991 ◽

pp. 389-391

Author(s):

R. Fety ◽

J. Vignoud ◽

P. Cappelaere ◽

A. Pineau ◽

P. Viau

Keyword(s):

Squamous Cell Carcinoma ◽

Adjuvant Chemotherapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Pharmacokinetic Study ◽

Neck Squamous Cell Carcinoma ◽

Neo Adjuvant Chemotherapy

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Nonsmoking and Nondrinking Oral Squamous Cell Carcinoma Patients: A Different Entity

Frontiers in Oncology ◽

10.3389/fonc.2021.558320 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhan Yang ◽

Wei Du ◽

Xu Zhang ◽

Defeng Chen ◽

Qigen Fang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Educational Background ◽

Hpv Infection ◽

Locoregional Control ◽

Disease Stage ◽

The Difference ◽

P16 Expression

ObjectiveOur goal was to analyze the demographic and pathologic characteristics as well as prognosis in nonsmoking and nondrinking (NSND) oral squamous cell carcinoma (SCC) patients compared with typical oral SCC patients.Patients and MethodsA total of 353 patients were retrospectively enrolled and divided into two groups: the NSND group and the current smoking/current drinking (CSCD) group. Demographic, pathologic, and molecular data were compared between the two groups. The main research endpoints were locoregional control (LRC) and disease-specific survival (DSS).ResultsIn the NSND group, 16.3%, 41.9%, and 53.5% of patients were aged no more than 40 years, were female, and had an educational background of high school or above compared to 3.7%, 6.0%, and 38.2% of patients in the CSCD group, respectively. A total of 15.1% of the NSND patients had SCC of the lower gingiva and floor of the mouth, which was lower than the 35.6% of patients in the CSCD group. CSCD patients were likely to have an advanced disease stage (48.7% vs 32.5%, p=0.042) and poorly differentiated cancer (26.6% vs 16.3%, p=0.042). The NSND patients had a mean Ki-67 index of 24.5%, which was lower than the mean of 35.7% in the CSCD patients. The two groups had no HPV infection and similar p16 expression (4.7% vs 10.1%, p=0.132), but there was higher expression of p53 (38.6% vs 17.4%, p<0.001) and p63 (59.9% vs 29.1%, p<0.001) in the CSCD group. The 5-year LRC rates for NSND patients and CSCD patients were 48% and 38%, respectively, and the difference was significant (p=0.048). The 5-year DSS rates for NSND patients and CSCD patients were 56% and 39%, respectively, and the difference was significant (p=0.047). Further, a Cox model confirmed the independence of smoking and drinking status for affecting LRC and DSS.ConclusionNSND oral SCC patients are a different entity. HPV infection has a limited role in carcinogenesis in NSND patients, and p16 expression is associated with worse locoregional control.

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Clinicopathological Study of Neo-adjuvant Chemotherapy for Oral Squamous Cell Carcinoma

The Journal of the Kyushu Dental Society ◽

10.2504/kds.51.761 ◽

1997 ◽

Vol 51 (6) ◽

pp. 761-767

Author(s):

Hideo Kurokawa ◽

Keiko Miura ◽

Yoshihiro Yamashita ◽

Shingo Tokudome ◽

Tomoyuki Murata ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Adjuvant Chemotherapy ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinicopathological Study ◽

Neo Adjuvant Chemotherapy

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Abnormal p16 Expression and Prognostic Significance in Chinese Esophageal Squamous Cell Carcinoma

10.21203/rs.3.rs-112931/v1 ◽

2020 ◽

Author(s):

Xue Zhang ◽

Weijie Chen ◽

Xiaolei Zhang ◽

Lei Xu ◽

Feng Gao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Disease Free Survival ◽

Negative Group ◽

Expression Status ◽

Focal Expression ◽

P16 Expression

Abstract Background: The purpose of this study was to analysis p16 expression status and evaluate whether abnormal p16 expression was associated with prognosis in a large-scale Chinese esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively evaluated p16 expression status of 525 ESCC samples using immunohistochemistry. Associations between abnormal p16 expression and survival were analyzed. Results: P16 negative, focal expression and overexpression were found in 87.6%, 6.9% and 5.5% of ESCC patients. No significant association was observed between abnormal p16 expression and age, sex, tumor site and location, differentiation, vessel and nerve invasion, T stage and lymph node metastasis. In all patients, the survival of p16 focal expression group tended to be better compared with negative group (disease free survival/DFS P=0.040 and overall survival/OS P=0.052) and overexpression group (DFS P=0.201 and OS P=0.258), and there was no survival difference between negative group and overexpression group. The multivariate analysis for OS and DFS only found clinical stage was a significantly independent prognostic factor (P<0.001). When patients were divided into I-II stage (n=290) and III-IVa stage (n=235), the survival of focal expression group was better compared with negative group (DFS P=0.015 and OS P=0.019), tended to be better compared with overexpression group (DFS P=0.405 and OS P=0.432) in I-II stage ESCC, which was not found in III-IVa stage ESCC.Conclusion: P16 overexpression or negative tend to be associated with unfavorable outcomes, especially in I-II stage ESCC. Our study will help to identify a subgroup of ESCC patients with excellent prognosis after surgical therapy.

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