HPV Virus Treatments - Knowledge

Aldrich T, Becker D, Garcia SG, Lara D. Population Council, Panzacola 62, Interior 102, Population Council, Col Villa Coyoacan, Mexico DF 04000, Mexico.

OBJECTIVE: To assess Mexican physicians' knowledge about the human papillomavirus (HPV) and cervical cancer and their opinions and practices related to screening, managing, and counselling women on these topics.Methodology: In August 2002 we surveyed 1206 general practitioners (GPs) and obstetricians-gynaecologists (Ob-Gyns) working in a nationally representative sample of public and private facilities in urban Mexico. Eligible physicians completed a self administered questionnaire. We conducted a weighted analysis and used chi(2) tests to compare GPs and Ob-Gyns on outcome variables. RESULTS: 76% of recruited physicians responded to the survey. 43% of Ob-Gyns had performed a hysterectomy in the last year to treat a case of CIN I or II. With respect to HPV, while 80% of respondents identified the virus as the principal cause of cervical cancer, many lacked detailed knowledge about this association. Ob-Gyns were more likely than GPs to have heard about specific oncogenic strains of HPV (p<0.001). Nearly all respondents thought that women should be informed that HPV causes cervical cancer; nevertheless, physicians believed that positioning cervical cancer as a sexually transmitted infection (STI) could cause problems in partner relationships (60%), confusion (40%), and unnecessary anxiety among women (32%). CONCLUSIONS: Mexican physicians support patient education on the HPV-cervical cancer link. However, findings suggest the need to present clear messages to women (emphasising, for example, that only certain types of HPV are oncogenic), to consider the conflicts such information might create for couples, and to further educate physicians about this topic and about overall cervical cancer screening and treatment protocols.

Vaccine. 2005 Mar 18;23(17-18):2388-94.

Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control.

Franco EL, Harper DM. Division of Cancer Epidemiology, Department of Oncology and Epidemiology, McGill University, 546 Pine Avenue West, Montreal, Que., Canada H2W 1S6. eduardo.franco@mcgill.ca

Universal deployment of organized or opportunistic screening with Pap cytology in high and middle income countries has been the primary reason for the substantial reductions in cervical cancer morbidity and mortality during the last 50 years. However, in many low income countries Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Cervical cancer thus remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. The fact that infection with certain human papillomavirus (HPV) types is now recognized as a necessary cause of this disease has led to new research fronts on the prevention of cervical cancer. Recent research on the safety and efficacy of candidate prophylactic vaccines against HPV have shown very promising results with nearly 100% efficacy in preventing the development of persistent infections and cervical precancerous lesions. Ongoing clinical studies are expected to provide further evidence of efficacy and will form the basis for licensing of candidate vaccines by the major pharmaceutical companies within 3-6 years. Although the future seems bright on the HPV vaccine front policy makers are strongly cautioned to avoid scaling back cervical cancer screening. It will take many years before we can rationally develop cervical cancer screening strategies that will be cost-effective for the proper surveillance of women protected by HPV vaccination.

Publication Types:
• Review
• Review, Tutorial

Expert Opin Emerg Drugs. 2005 Feb;10(1):5-19.

Emerging human papillomavirus vaccines.

Christensen ND. The Pennsylvania State University College of Medicine, The Department of Microbiology and Immunology, Hershey, PA 17033, USA. ndc1@psu.edu

Human papillomavirus (HPV) infections are a leading cause of virus-associated cancers of the anogenital, oropharyneal and cutaneous epithelium. The most prevalent of these is cervical cancer, which is responsible for approximately 500,000 deaths annually worldwide. A group of about 15 serologically unrelated 'high-risk' HPV types are responsible for almost all HPV-associated cancers. Prevention of papillomavirus infection can be achieved by induction of capsid-specific neutralising antibodies in preclinical animal papillomavirus models and in recent human clinical trials. High titres of conformationally-dependent, type-specific HPV-neutralising antibodies are triggered by HPV virus-like particle (VLP) vaccines. Overcoming the problems of type-specificity of the responses to these VLP vaccines is a potentially important area of current HPV vaccine research, with an emphasis on induction of more broadly cross-protective neutralising responses. Viral oncogenes E6 and E7 are continuously present in HPV-associated cancers and are prime targets for HPV therapeutic vaccines. A variety of approaches are being tested in therapeutic vaccine clinical trials and in various preclinical animal papillomavirus models for efficacy. Approaches include genetic vaccines, recombinant virus vaccines, dendritic cell-based strategies, immunomodulatory strategies and various combination strategies to maximise cell-mediated immunity to papillomavirus proteins present in HPV infections and cancers. The success of preventive HPV VLP vaccines in clinical trials is clear. However, current therapeutic vaccine trials are less effective with respect to disease clearance. Nevertheless, a series of combination approaches have shown significant therapeutic enhancement in preclinical papillomavirus models and await testing in patient populations to determine the most effective strategy. There is much encouragement that HPV vaccines will be the most effective approach to prevention and cure of infections caused by this group of viruses, which re-present a significant human pathogen.

Cancer Genet Cytogenet. 2005 Apr 1;158(1):35-42.

cDNA array analysis of cytobrush-collected normal and malignant cervical epithelial cells: a feasibility study.

Hudelist G, Czerwenka K, Singer C, Pischinger K, Kubista E, Manavi M. Department of Gynecology and Obstetrics, Division of Special Gynecology, University of Vienna Medical Center, Vienna, Austria.

Analysis of gene expression pattern is a useful approach to evaluating the biological behavior and clinical outcome of several human malignancies. Differentially expressed genes in malignant squamous cervical cells and the feasibility of gene expression profiling on squamous cervical cells obtained from cervical swabs were investigated. Cervical squamous cells from three women with high-risk human papilloma virus (HR-HPV) positive invasive squamous cervical carcinoma and from three HPV-negative women with normal ectocervical smears were analyzed with cDNA array. Immunoblot analysis was performed to detect the proteins corresponding to the highest upregulated genes with cDNA array. mRNA expression of ERBB2, KIT, FLT1, MYCN, RAS, CDKN2A, CCND1, NME1, NME2, MET, FGF7, FGFR2, and STAT1 was increased in malignant samples. Several expressed genes associated with antiapoptosis (such as BCL2), cell structuring, or cell attachment were also upregulated in carcinoma cells. Decreased gene expression was observed for members of the transforming growth factor receptor superfamily (TGF) and integrin family, interleukin 1 (IL1), and insulin-like growth factor binding proteins (IGFBPs). This study shows the feasibility of gene expression profiling of cervical squamous cells obtained with cytobrushes by identifying a characteristic gene expression pattern that clearly distinguishes between malignant and normal cervical epithelia of squamous type. We hypothesize that this noninvasive technique could be used in the evaluation of ambiguous Papanicolaou (PAP) smears.

Gynecol Oncol. 2005 Apr;97(1):142-50.

Sensitization of cervical cancer cell lines to low-dose radiation by retinoic acid does not require functional p53.

Tillmanns TD, Kamelle SA, Guruswamy S, Gould NS, Rutledge TL, Benbrook DM. Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.

OBJECTIVE: Current therapy for cervical cancer includes radiation therapy. Retinoic acid (RA) can increase the sensitivity of cervical cancer cell lines to radiation. The mechanism of this sensitization may not involve the p53 protein because the human papillomavirus (HPV) E6 protein, which is present in the majority of cervical cancers, promotes p53 degradation. The objective of this study was to determine if p53 is involved in the mechanism of RA radiosensitization. METHOD: The effects of radiation on cervical (SiHa, CC-1, and C33a) and vulvar (SW962) cancer cell lines under various experimental conditions were evaluated using clonogenic, Coulter Counter, electrophoretic mobility shift (EMSA) and a multi-probe RNase protection assay of p53-inducible genes. RESULTS: RA (5 microM 9-cis-RA) radiosensitized the SiHa and CC-1 cell lines that contain HPV-degraded p53, but did not radiosensitize the SW962 cell line, which is HPV negative and contains wild-type p53, nor the C33a cell line, which contains mutant p53 (R273C). Expression of mutant p53 (R273H) in SiHa cells increased the growth rate, but did not prevent RA-induced differentiation or radiosensitization at clinically relevant doses. Inhibition of p53 transactivation with pifithirin alpha did not prevent RA radiosensitization of SiHa at 5 Gy. RA repressed c-fos mRNA expression in control and irradiated SiHa cultures, but did not repress bcl-x(L), p53, GADD45, p21, bax, bcl-2, or mcl-1 mRNA expression. CONCLUSIONS: The mechanism of RA radiosensitization does not require functional p53 and may involve c-fos in cervical cancer cell lines.

HPV Virus Treatments - HPV Knowledge Links

Awareness of Human Papillomavirus - An article assessing the level and accuracy of public understanding of human papillomavirus (HPV) in the United Kingdom.

Genital Warts and HPV - A general genital warts overview.