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   2009| September  | Volume 130 | Issue 3  
    Online since April 20, 2011

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The magnitude of cancer cervix in India
A Nandakumar, T Ramnath, M Chaturvedi
September 2009, 130(3):219-221
The Indian Council of Medical Research initiated a network of cancer registries under the National Cancer Registry Programme (NCRP) in 1981 and data collection commenced in these registries from January 1982. The results on incidence rates provided by the Population Based Cancer Registries (PBCRs) have shown the variation in patterns of cancer in general and that of cancer cervix in particular. Cancer of the cervix has been the most important cancer in women in India, over past two decades. All the urban Population Based Cancer Registries at Bangalore, Bhopal, Chennai, Delhi and Mumbai have shown a statistically significant decrease in incidence rates of this site of cancer. Since over 70 per cent of the Indian population resides in the rural areas, cancer cervix still constitutes the number one cancer in either sex. Based on the data of the PBCRs, the estimated number of new cancers during 2007 in India was 90.708. The relative five year survival reported some time earlier averaged 48.7 per cent.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Infection of human papillomaviruses in cancers of different human organ sites
S Shukla, Alok C Bharti, S Mahata, S Hussain, R Kumar, S Hedau, Bhudev C Das
September 2009, 130(3):222-233
Clinico-epidemiological and molecular studies have established the casual link between Human Papillomavirus (HPV) infection and cervical cancer as also association of HPV infection with several other cancers. In India, cervical cancer is a leading cancer among women and almost all cases of cervical cancer show prevalence of High Risk (HR)-HPV infection. HPV has been also detected in a significant proportion of oral, esophageal, anal, vaginal, vulvar, and penile cancer and in a small percentage of lung, laryngeal, and stomach cancer in India. Due to lack of organized HPV screening program, insufficient infrastructure and trained manpower and inadequacy in cancer registries, there are not much data available on the countrywide HPV prevalence and its type distribution in different cancers in India. Forthcoming introduction of recently developed HPV vaccines in India given a new urgency to know the prevalence and distribution of various HPV types in different organ sites for the management and monitoring of vaccination program and its impact on prevalence of other cancers. This review, summarizes studies on the prevalence of HPV infection in cancers of different organ sites in India.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Human papillomavirus vaccines : current issues & future
K Kawana, T Yasugi, Y Taketani
September 2009, 130(3):341-347
Cervical cancer is the leading cause of cancer mortality among women in worldwide. Some 99 per cent of cervical cancer cases are linked to genital infection with human papillomaviruses (HPVs) comprised of approximately 15 oncogenic genital HPV types. Most HPV infections resolve spontaneously. But, the remainder persist and may then progress to cervical cancer in some women. In high-resource countries, the best way to prevent cervical cancer is to implement organised gynaecological screening programs with appropriate treatment of the detected pre-cancerous lesions. However, in developing countries, this method is not practicable because of cost and complexity of proper screening. Vaccines against HPV infections hold promise to reduce incidence of cervical cancer cost-effectively. Two Prophylactic HPV vaccines have been thus far developed: Gardasil(R), a quadrivalent vaccine targeting HPV-6, -11, -16 and -18) and Cervarix(R), a bivalent vaccine which targets HPV-16 and -18. Both vaccines contain L1 virus-like particles (VLPs) derived from HPV-16 and -18 which are most frequently associated with cervical cancer. The L1-VLP vaccines are HPV type-specific and therefore can effectively prevent infection of a HPV type in question alone. Therefore, the L1-VLP vaccines are hoped to be multivalent for 15 oncogenic HPV types, which comes at a price. Otherwise, costly cytologic screening for cervical cancer is still necessary. The current HPV vaccines thus may not be ultimate strategy and study on new HPV vaccines is needed. Broad-spectrum prophylactic vaccines against all oncogenic HPV types and therapeutic vaccines for clearance of HPV-related cervical lesion are being developed.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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HPV & HPV vaccination : issues in developing countries
M Bharadwaj, S Hussain, V Nasare, Bhudev C Das
September 2009, 130(3):327-333
Cervical cancer is the second-most common cancer in women worldwide causing most cancer related deaths in women in developing countries including India. The most predominant etiological factor for cervical cancer is persistent infection of certain high-risk types of human papillomaviruses (HR-HPVs), while low-risk types are associated with benign cervical lesions and genital warts. In India, the most common (98%) oncogenic types are HPV types 16 and 18 with HPV 16 exclusively (80-90%) prevalent. Two recently developed virus-like particle (VLP) based prophylactic HPV vaccines, quadrivalent Gardasil (HPV 16/18/6/11) and Cervarix (HPV 16/18) offer great promise. Several other therapeutic vaccines are also in clinical trials and are yet to establish their efficacy. The use of already developed VLP vaccines in resource-poor regions is limited by several factors, most importantly the high cost of the vaccine. Therefore efforts are being made in India to develop cost-effective second-generation vaccines. Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Cervical cancer screening & HPV vaccination : a comprehensive approach to cervical cancer control
P Basu, D Chowdhury
September 2009, 130(3):241-246
India with its highest share of global burden of cervical cancer has to implement a population based cervical cancer control program to reduce the number of deaths. There are new screening options available like visual inspection after acetic acid application (VIA) test, single visit approach to screening and treatment etc. Emergence of the two effective vaccines against human papillomavirus (HPV), the necessary cause of cervical cancer, has introduced a fresh lease of life to the cervical cancer control strategies. The current high cost of the vaccines is a major impediment to implement a vaccine-based primary prevention approach.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Anti-human papillomavirus therapeutics : facts & future
Alok C Bharti, S Shukla, S Mahata, S Hedau, Bhudev C Das
September 2009, 130(3):296-310
Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dys-regulate the host cell cycle following transformation is discussed.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Human papillomavirus infection (HPV) & screening strategies for cervical cancer
A Sehgal, V Singh
September 2009, 130(3):234-240
The incidence of cervical cancer is declining slowly necessitating concerted and organized control measures. Control through primary prevention has become a distinct reality though a prophylactic vaccine, which may take quite some time for its widespread use. Thus control of cervical cancer through secondary preventive measures is the only viable solution now. While high quality cytology screening may not be feasible for widescale implementation in developing countries because of lack of necessary infrastructure, quality control and poor sensitivity of cytology, alternative screening modalities such as visual screening techniques and HPV-DNA can be explored. Some technical and feasibility aspects of these three modalities are discussed.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Cervical cancer prevention & the role of human papillomavirus vaccines in India
N Bhatla, E Joseph
September 2009, 130(3):334-340
Human papillomavirus (HPV) is a necessary cause of cervical cancer, the leading cause of cancer deaths among Indian women. Current screening and prevention programs based on cytology have not been effective in reducing the disease burden. Two vaccines are now available for primary prevention. They generate neutralizing antibodies to HPV capsid protein. The vaccines have been shown to confer nearly 100 percent protection against cervical pre-cancers and genital warts caused by HPV types 16/18 in HPV naïve population with few or no side effects. Though there is some cross-protection, around 30 percent of cervical cancers will not be prevented by the vaccine. Vaccination and screening, which are complementary and synergistic, now constitute the new paradigm for prevention of this disease.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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HPV vaccination : the promise & problems
R Sankaranarayanan
September 2009, 130(3):322-326
Four-fifths of the cervical cancer burden in the world is experienced in developing countries. HPV genotypes 16 and 18 account for 70 per cent of cervical cancers and currently available vaccines targeting these two types confer a high degree of protection against HPV 16/18 infection and related cervical precancerous lesions. However, widespread implementation of HPV vaccination programs are challenged by the unaffordable high costs of the vaccines and the lack of effective vaccine delivery platforms for sexually naïve girls. Other unresolved issues include long-term protection, cross-protection against HPV types not included in the vaccine and whether booster doses will be needed. Sensitivities associated with a vaccine preventing a sexually transmitted infection in girls, lack of awareness, public demand and political will, lack of coordination between cancer control, sexual and reproductive health and vaccine delivery services are additional challenges. Reduced costs, simple vaccine regimes and strengthening vaccine delivery platforms for adolescents should eventually facilitate HPV vaccine introduction in developing countries.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Genotypes of the human papillomavirus : relevance to Indian field trials of the vaccine
I Hariharan, M Radhakrishna Pillai
September 2009, 130(3):247-260
Highly effective HPV vaccines are likely to become available for use in India shortly. The availability and validation of the vaccines to prevent oncogenic HPV infection associated lesions from progressing to cancer has clearly offered a cost effective long-term strategy to reduce the cervical cancer burden, particularly for developing countries where effective screening programmes are not available. The enthusiasm for these new vaccines duly justified, are we in reality targeting the actual delinquent by prompting these vaccines in India? The answer would be no as we may not be essentially implementing a rational fool-proof vaccine program which will aid in preventing HPV-related diseases, for the simple reason that there is a lack of understanding about the underlying HPV types responsible for cervical cancer in India. Field trials involving large populations form a major part of continued analysis in understanding any disease and India is still short of such a trial as far as cervical cancer is concerned. Conducting such studies, might also act as prevention programs that will save lives and improve public health in a substantive manner.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Immune responses to human papilloma viruses
MA Stanley
September 2009, 130(3):266-276
HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune response and the lesions regress. Regression of ano-genital warts is accompanied histologically by a CD4+ T cell dominated Th1 response; animal models support this and provide evidence that the response is modulated by CD4+ T cell dependent mechanisms. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The central importance of the CD4+ T cell population in the control of HPV infection is shown by the increased prevalence of HPV infections and HGSIL in individuals immunosuppressed as a consequence of HIV infection. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity as reflected in the absence of inflammation during virus replication, assembly and release, and down regulation of interferon secretion and response thus delaying the activation of adaptive immunity. Serum neutralising antibody to the major capsid protein L1 usually develops after the induction of successful cell mediated immunity and these antibody and cell mediated responses are protective against subsequent viral challenge in natural infections in animals. Prophylactic vaccines consisting of HPV L1 VLPs generate high anti L1 serum neutralizing antibody concentrations and in clinical trials have shown greater than 95 per cent efficacy against both benign and neoplastic genital HPV associated disease. These vaccines are delivered intramuscularly and therefore circumvent the immune evasion strategies of the virus.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
  175 122 -
The clinical utility of HPV DNA testing in cervical cancer screening strategies
N Bhatla, N Moda
September 2009, 130(3):261-265
Cervical cancer continues to be the commonest cause of death among women in developing countries, largely due to the failure to the inability to sustain effective cytology-based screening programs. While this burden may come down following implementation of the human papillomavirus (HPV) vaccine, screening will still be required. HPV DNA testing is a promising new technology for cervical cancer prevention and is the most reproducible of all cervical cancer screening tests. Presently, the two assays most widely used for the detection of genital types are the polymerase chain reaction (PCR) and Hybrid Capture 2 assays (hc2). Rapid, affordable tests are expected to be available soon. HPV DNA testing can be used in a variety of clinical scenarios that include primary screening in women older than 30 yr; as an adjunctive test to cytology; in the triage of women with an equivocal cytologic report, e.g., ASC-US; or for follow-up post-treatment for cervical intraepithelial neoplasia (CIN). HPV DNA testing can also be performed on self-collected samples, which allows screening in remote areas and also in women who refuse gynecologic examination.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
  183 111 -
Cell intrinsic & extrinsic factors in cervical carcinogenesis
RS Jayshree, A Sreenivas, M Tessy, S Krishna
September 2009, 130(3):286-295
Human papillomavirus (HPV) infection is a common sexually transmitted infection which a majority of infected women are able to clear by mounting an effective immune response. Individuals with a suboptimal immune response may be at increased risk of persistent HPV infection leading to sequelae of various grades of dysplasias and / or associated malignancy. Both cell intrinsic and extrinsic phenomena work in concert to bring about oncogenesis. Cell intrinsic factors for cervical carcinogenesis are: integration of the viral genome into the genome of the host's cell which correlates with the progression of low grade lesions into high grade ones, inactivation of tumor suppressor genes like p53 and pRB by HPV oncoproteins particularly E6 and E7, deregulation of cell cycle regulators, host DNA synthesis and apoptosis. Cell extrinsic elements include factors contributing towards immune tolerance; some incriminated in the multistep carcinogenesis of HPV induced cervical cancer are: immunoregulatory enzyme indoleamine 2,3-dioxygenase expressing antigen presenting cells, low numbers of invariant Natural Killer T cells, anergic cytotoxic T lymphocytes, regulatory T cells (Tregs), an immunoregulatory microenvironment comprising of increased IL10, TGF and reduced IL2; reduced intralesional ratios of effectors (CD4 and CD8) vs. Tregs; and different types of Tregs in the lesions of invasive squamous cell carcinoma. Notch signaling plays a crucial role in regulating T cell differentiation and activation including induction of Tregs. Increased expression of Notch receptor-Jagged 1 and number of Tregs were seen in invasive disease when compared to precancer in cervical cancer. Tregs impart their function either through cytokines or by cell to cell contact. Investigation of the consequences of interference of Notch signaling in terms of the dynamics of intratumoral Tregs in cervical cancer would be interesting.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Can cervical cancer be eradicated by prophylactic HPV vaccination? Challenges to vaccine implementation
Suzanne M Garland
September 2009, 130(3):311-321
Cervical cancer is the first cancer to be shown to be 100 per cent attributable to a virus; oncogenic human papillomaviruses (HPV), particularly types 16 and 18, collectively worldwide contribute to 70 per cent squamous cell carcinomas, 85 per cent of adenocarcinomas. Cervical cancer is the second commonest cancer of women, yet largely preventable with high-quality, well-organized screening of the appropriate population. Screening programmes are either nonexistent, or function opportunistically in many poorer countries, resulting in high incidence and mortality. Recently developed, prophylactic HPV vaccines against HPV 16, 18, as cervical cancer preventative vaccines, in phase 3 clinical trials have been shown, to be highly efficacious, safe and immunogenic. With the potential for cross protection against related HPV types, estimates for prevention are in the order of 75 to 80 per cent. Thus a further option exists in the battle to reduce these cancers in women. Challenges however include implementing a vaccination programme with wide coverage to the target populations to be a successful public health tool, integration and maintenance of current screening programmes where they are in existence, the need for reduced costs of the current vaccines, long-term immunogenicity (will there be a need for further doses?), appropriate education messages to the general community, governments, as well as the medical profession.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
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Human papillomavirus infection, cancer & therapy
Helena Sterlinko Grm, M Bergant, L Banks
September 2009, 130(3):277-285
Infection with human papillomaviruses (HPVs) is a major public health burden worldwide and is associated with a variety of epithelial lesions, including benign warts and several types of anogenital tumours, particularly cervical carcinoma. From available data it is clear that members of the HPV family are important human pathogens. Prevention or elimination of these infections would not only benefit the numerous patients with benign lesions, but ultimately should reduce the incidence of cervical cancer and possibly other epithelial cancers as well. Although prophylactic vaccines to block genital HPV infection have become available, it is not certain if they would be of benefit to those already infected. Therefore, the enormous and growing population of infected individuals would benefit from papillomavirus-specific therapy. In this review, we will discuss the functions of the viral proteins that appear to be the most appropriate for the development of therapeutics aimed at the treatment of viral infection and virus-induced cancers.
[ABSTRACT]   Full text not available  [PDF]  [PubMed]
  181 98 -
Production of immunogenic human papillomavirus-16 major capsid protein derived virus like particles
Mira C Patel, Ketaki K Patkar, A Basu, KM Mohandas, R Mukhopadhyaya
September 2009, 130(3):213-218
Full text not available  [PDF]  [PubMed]
  136 128 -
Human papillomavirus & cervical cancer
H zur Hausen
September 2009, 130(3):209-209
Full text not available  [PDF]  [PubMed]
  118 119 -
Human papillomavirus & cervical cancer : looking ahead
Bhudev C Das, Alok C Bharti, M Bharadwaj
September 2009, 130(3):210-211
Full text not available  [PDF]  [PubMed]
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Some Forthcoming Scientific Events

September 2009, 130(3):348-349
Full text not available  [PDF]
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September 2009, 130(3):349-349
Full text not available  [PDF]
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