HPV and p53 expression in epithelial ovarian carcinoma

Objectives: Human papillomavirus is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear. This study aimed to determine the presence of human papillomavirus (HPV) in ovarian cancer tissues along with the expression of tumor suppressor gene p53. We also investigated any possible association of HPV with p53 gene mutations in ovarian carcinoma.

Methods: Archived human ovarian cancer tissues (n = 40 cases of epithelial ovarian cancer) embedded in paraffin blocks were used. Controls were 32 non-malignant ovarian tumor tissue blocks. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the presence of HPV and p53 expression, respectively.

Results: Of the total, 37.5% (n = 15) of malignant and 28.1% (n = 9) of benign ovarian tumors were positive for HPV (OR: 1.5 CI: 0.5-4.1, p = 0.4). The difference was not statistically significant. However, p53 was detected in 72.5% (n = 29) of malignant cases compared to 37.5% (n = 12) of benign cases (OR: 4.3 CI: 1.6-11.9, p = 0.003). Furthermore, a positive correlation between HPV and p53 expressions in ovarian cancer tissue samples was detected (r = 0.47, p = 0.001).

Conclusions: HPV does not seem to be a major component in the development of ovarian carcinoma, nevertheless HPV positivity seems to contribute to the pathogenesis in at least some ovarian carcinoma cases by way of interaction with tumor suppressor p53.

HPV; p53; Ovarian carcinoma; Immunohistochemistry; In situ hybridization

[1] Bosch F.X., de Sanjose S.: "Human papillomavirus in cervical cancer". Curr. Oneal. Rep., 2002, 4, 175.

[2] Bosch F.X., Lorincz A., Munoz N., Meijer CJ., Shah K.Y.: "The causal relation between human papilloma virus and cervical cancer". J. Clin. Pathol., 2002, 55, 244.

[3] Ferenczy A. Franco E.: "Persistent human papillomavirus infection and cervical neoplasia" Lancet Oncol., 2002, 3, 11.

[4] Milde-Langosch K., Becker G., Loning T.: "Human papilloma virus and c-myc/c-erbB2 in uterine and vulvar lesions". Virchows Areh. A. Pathol. Anal. Histopathol., 1991, 419, 479.

[5] Badaracco G., Venuti A., Sedati A., Marcante M.L.: "HPV 16 and HPV 18 in genital tumors: Significantly different levels of viral " integration and correlation to tumor invasiveness". J. Med. Viral., 2002, 67, 574.

[6] Lai C.H.,H sueh S., Lin C.Y.,H uang M.Y.,Y ou G.B.,C hang H.C. et al.: "Human papillomavirus in benign and malignant ovarian and endometrial tissues". Int. J. Gynecol. Pathol., 1992, 11, 210.

[7] Anwar K., Nakakuki K., Imai H., Shiraishi T., lnuzuka M.: "Infection of human papillomavirus (HPV ) and p53 over expression in human female genital tract carcinoma". J. Pak. Med. Assoc., 1996, 46, 220.

[8] Beckmann A.M., Sherman K.J., Saran L., Weiss N.S.: "Genital type human papillomavirus infection is not associated with surface epithelial ovarian carcinoma". Gynecol. Oncol., 1991, 43, 247.

[9] Cotran R.S., Kumar V., Collins T.: "Robbins pathologic basis of disease, neoplasia". In: Cotran R.S., Kumar V., Collins T. (eds.). Robbins Pathologic Basis of Disease, 6th ed山on,Philadelphia, W.B. Saunders, 1999, 290.

[10] Sherr C.J.: "Gl phase progression: Cycling on cue". Cell, 1994, 79, 551.

[11] Miyashita T., Krajewski S., Krajewska M., Wang H.G., Lin H.K., Liebermann D.A. et al.: "Tumour suppressor p53 is a regulator of bcl-2 and base gene expression in vitro and in vivo". Oncogene, 1994, 9, 1799.

[12] Dyson N., Howley P.M., Munger K., Harlow E.: "The human papilloma virus-16 E7-oncoprotein is able to bind to the retinoblastoma gene product". Science, 1989, 243, 934.

[13] Scheffner M., Werness B.A., Huibregtse J.M., Levine A.J., Howley P.M.: "The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53". Cell, 1990, 63, 1129.

[14] Wu Q.J., Guo M., Lu Z.M., Li T., Qiao H.Z., Ke Y.: "Detection of human papilloma virus-16 in ovarian malignancy". Br. J. Cancer., 2003, 89, 672.

[15] Li T., Lu Z.M., Guo M., Wu Q.. J., Chen K.N., Xing H.P., et al.: "p53 codon 72 polymorphism (C/G) and the risk of human papilIomavirus-associated carcinomas in China". Cancer, 2002, 95, 2571.

[16] Pestell K.E., Hobbs S.M., Titley J.C., Kelland L.R., Walton M.I..: "Effect of p53 status on sensitivity to platinum complexes in a human ovarian cancer cell line". Mo/. Pharmacol., 2000, 57, 503.

[17] Gupta J., Pilotti S., Rilke F., Shah K.: "Association of human papillomavirus type 16 with neoplastic lesions of the vulva and other genital sites by in situ hybridisation". Am. J. Pathol., 1987, 127, 206.

[18] Kaufman R.H., Bornstein J., Gordon A.N., Adam E., Kaplan A.L., Adler-Storthz K.: "Detection of human papillomavirus DNA in advanced epithelial ovarian carcinoma". Gynecol. Oneal., 1987, 27, 340.

[19] Anttila M., Syrjanen S., Ji H., Saarikoski S., Syrjanen K.: "Failure to demonstrate human papillomavirus DNA in epithelial ovarian cancer by general primer PCR". Gynecol. Oncol., 1999, 72, 337.

[20] Crook T., Wrede D., Tidy J.A., Mason W.P., Evans D.J., Vousden K.H.: "Clonal P53 mutation in primary cervical cancer: association with human papillomavirus-negative tumours". Lancet, 1992, 339, 1070.

[21] Kmet L.M., Cook L.S., Magliocco A.M.: "A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors". Cancer, 2003, 97, 389.

[22] Ku J.L., Kim W.H., Park H.S., Kang S.B., Park J.G.: "Establishment and characterization of 12 uterine cervical carcinoma celllines: common sequence variation in the E7 gene of HPV 16-positive cell lines". Int. J. Cancer, 1997, 72, 313.

[23] Thomas M., Pim D., Banks L.: "The role of the E6-p53 interaction in the molecular pathogenesis of HPV". Oncogene, 1999, 15, 7690.