HPV Virus Infections - Cancer

Sano T, Masuda N, Oyama T, Nakajima T. Second Department of Pathology, Gunma University School of Medicine, Showa-machi, Maebashi, Japan. sanot@gunma-u.ac.jp

The CDKN2 gene encodes two structurally different proteins: a cyclin-dependent kinase inhibitor, p16, which regulates retinoblastoma protein (pRb)-dependent G1 arrest, and a cell cycle inhibitor, p14ARF, which blocks MDM2-induced p53 degradation resulting in an increase in p53 levels that leads to cell cycle arrest. Recent studies have revealed that expression of p16 and p14ARF is influenced markedly by the status of pRb and p53, and p16 overexpression has been demonstrated in cervical neoplasia because of functional inactivation of pRb by the human papillomavirus (HPV) E7 protein. To clarify the p14ARF status and the relationship between p16/p14ARF and other cell cycle molecules in cervical carcinogenesis, immunohistochemical analysis of p16, p14ARF, p53 and MDM2 was performed on 65 samples of cervical and genital condylomatous and neoplastic lesions, including nine HPV-negative tumors. In most cervical cancers and preneoplastic lesions with HPV infection of high and intermediate risk, a marked overexpression of p14ARF as well as the p16 protein (i.e. dotted nuclear immunostaining) was observed. All condyloma acuminata except one and low-grade dysplasia with HPV infection of low risk, such as HPV 6, immunohistochemically showed completely negative staining for p14ARF, also seen in non-neoplastic and mesenchymal cells. Our results clearly show that the mode of p14ARF overexpression in cervical neoplastic cells with HPV association differs from that in cancers of other organs without HPV association, and the p14ARF overexpression may be attributable to a negative feedback result in the functional inactivation of the pRb and p53 proteins by HPV oncoproteins.

Ginekol Pol. 2002 Mar;73(3):167-70.

Identification of encoding and regulatory sequences of RAR-alpha receptor in intraepithelial neoplasia and in invasive cervical carcinomas associated with HPV types 16 and 18

HPV Virus Infections - Article in Polish

The purpose of the study was the analysis of regulatory (region 5 gen) and encoding sequences of RAR-alpha receptor in cervical dysplasia and invasive cancer associated with HPV infection. A PCR method with the use of specific primers was applied to amplify and detect DNA sequence of various HPV types. A PCR-SSCP method was used to analyse the sequence of RAR--a receptor. The study revealed changes in structure of regulatory and encoding sequences of the investigated RAR receptor. Utmost changes were found in DNA isolated from tissues with diagnosis of adenocarcinoma colli uteri.

Postgrad Med J. 2002 Apr;78(918):225-8.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

Jastreboff AM, Cymet T. University of Maryland School of Medicine Family Medicine, USA.

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

Publication Types:
• Review
• Review, Tutorial

J Cutan Med Surg. 2001 Jul-Aug;5(4):323-8. Epub 2001 Jul 18.

Human papillomavirus, smoking, and cancer.

Moore TO, Moore AY, Carrasco D, Vander Straten M, Arany I, Au W, Tyring SK. Department of Surgery, Baylor University Hospital, Dallas, TX, USA.

BACKGROUND: The effect of smoking on human papillomavirus (HPV) activity and subsequent dysplasia and neoplasia remains controversial. OBJECTIVE: To determine any reported effects of smoking on either HPV activity or HPV-related dysplasia/cancer using retrospective analysis of the literature from 1966 through 1998 via Toxline and PubMed to search for "smoking," "papillomavirus," and "cancer." CONCLUSION: Several recent large studies demonstrated that smoking was associated with a greater incidence of cervical, vulvar, penile, anal, oral, and head and neck cancer in a dose-dependent fashion, while other studies did not show any correlation between smoking and cervical dysplasia after multivariate adjustment. Recent studies have also indicated that smoking may be more closely related to high-grade lesions of the cervix and vulva. These data provide evidence of an association between HPV, smoking, and cancer. Progression of dysplasia likewise seems to be associated with smoking. Several groups have attempted to discern whether the connection between smoking and cervical cancer is from local immunosuppression and/or from direct carcinogenic effects.

Publication Types:
• Review
• Review, Tutorial

HPV Virus Infections - HPV and Cancer Links

Anogenital Cancer - A survey on etiology and prognosis of anogenital cancer.

Cancer of the Cervix - Consequences of treatments and survival rates in women with cervical cancer are presented in the article.