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The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.

Publication ,  Journal Article
Pillai, MR; Halabi, S; McKalip, A; Jayaprakash, PG; Rajalekshmi, TN; Nair, MK; Herman, B
Published in: Cancer Epidemiol Biomarkers Prev
May 1996

Cervical cancer is the second leading cause of death from cancer in women worldwide, and recent epidemiological studies have strongly implicated the sexually transmitted human papillomavirus (HPV) as a causative agent. The ability of high-risk HPVs to contribute to malignant progression seems to depend on expression of the viral E6 and E7 oncogenes. The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. J. Cell. Biochem., 57: 509-520, 1995). Based on these findings, we examined Papanicolaou smears from 94 women with varying degrees of cervical disease for the presence or absence of p53, HPV-16/18 E6, and bcl-2 proteins using immunofluorescence microscopy. Our findings indicate that there is a statistically significant, inverse association between the presence of p53 and invasive cervical disease [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7]. Moreover, the odds of being diagnosed with an invasive stage of cervical cancer were 3.7 times higher (95% CI, 1.6-8.8) for women positive for the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the bcl-2 protein compared with women negative for E6 and bcl-2. Women with invasive cervical cancer were also 4.59 times more likely to test positive for the presence of more than one marker (95% CI, 1.8-11.8). Chi(2) analysis demonstrated a strong association between the presence of E6 and bcl-2 (P < 0.001) as well as between the presence of E6 of bcl-2 and diagnosis (P = 0.015 and < 0.001, respectively). In the multivariate analysis, the presence of bcl-2 (OR, 18.8; 95% CI, 5.5-67.8) and age at diagnosis (> or = 50 years; OR, 7.8; 95% CI, 2.5-24.5) showed significant association with Invasive cervical disease. These findings indicate that: (a) the presence of the bcl-2 protein is strongly associated with the development of invasive cervical disease: (b) the pattern of the presence of high-risk HPV-E6, p53, and bcl-2 proteins may be useful for identifying women at increased risk for the development of invasive cervical cancer; and (c) a defect in apoptosis may partially underlie the development of cervical cancer.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

ISSN

1055-9965

Publication Date

May 1996

Volume

5

Issue

5

Start / End Page

329 / 335

Location

United States

Related Subject Headings

  • Vaginal Smears
  • Uterine Cervical Neoplasms
  • Ubiquitins
  • Tumor Virus Infections
  • Tumor Suppressor Protein p53
  • Repressor Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Protein-Tyrosine Kinases
  • Papillomavirus Infections
  • Papillomaviridae
 

Citation

APA
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ICMJE
MLA
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Pillai, M. R., Halabi, S., McKalip, A., Jayaprakash, P. G., Rajalekshmi, T. N., Nair, M. K., & Herman, B. (1996). The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer. Cancer Epidemiol Biomarkers Prev, 5(5), 329–335.
Pillai, M. R., S. Halabi, A. McKalip, P. G. Jayaprakash, T. N. Rajalekshmi, M. K. Nair, and B. Herman. “The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.Cancer Epidemiol Biomarkers Prev 5, no. 5 (May 1996): 329–35.
Pillai MR, Halabi S, McKalip A, Jayaprakash PG, Rajalekshmi TN, Nair MK, et al. The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer. Cancer Epidemiol Biomarkers Prev. 1996 May;5(5):329–35.
Pillai, M. R., et al. “The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.Cancer Epidemiol Biomarkers Prev, vol. 5, no. 5, May 1996, pp. 329–35.
Pillai MR, Halabi S, McKalip A, Jayaprakash PG, Rajalekshmi TN, Nair MK, Herman B. The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer. Cancer Epidemiol Biomarkers Prev. 1996 May;5(5):329–335.

Published In

Cancer Epidemiol Biomarkers Prev

ISSN

1055-9965

Publication Date

May 1996

Volume

5

Issue

5

Start / End Page

329 / 335

Location

United States

Related Subject Headings

  • Vaginal Smears
  • Uterine Cervical Neoplasms
  • Ubiquitins
  • Tumor Virus Infections
  • Tumor Suppressor Protein p53
  • Repressor Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Protein-Tyrosine Kinases
  • Papillomavirus Infections
  • Papillomaviridae