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Thursday, 14 November 2013

An ounce of prevention?

  1. Professor Pranab Kumar Bhattacharya








     said:
    We must await the collection of further epi, Including Grademiological data during coming decades for HPV vaccinesdsil
     Authors 
    Professor Pranab Kumar Bhattacharya, Rupak Bhattacharya & Miss Upasana Bhattacharya Professor Harald zur Hausen , did first identified human papilloma viruses as a key contributors to cervical cancer instead of HSV2 and had been awarded Nobel prize in medicine-2008. Cervical cancer is the second most common cancer among women world wide, with about 5,00,000 new cases each year with around 2,00,000 deaths a year in 3rd world countries compared with 70,000 in developed worlds1. Establishment of causal links between high-risk human papilloma viruses (HPV) and cervical cancer today however can set the basis for new areas of research that include the application of HPV testing and a low cost biomarkers to identify women at high risk of progression to cervical cancer and its precursors. Testing for high-risk HPV by Insitu Hybridization or by Immunohistochemistry in vaginal cytology is more sensitive and has a higher negative predictive value to detect the immediate precursors of cervical cancer (high-grade cervical intraepithelial neoplasia; CIN2/3) than conventional PAP cervical cytology, at the cost of a small decrease in specificity and positive predictive value. higher sensitivities for HPV antigens were noted for any of the DNA-based screening tests and liquid-based cytology is very much costly and technology based. Before administration of HPV vaccines a thorough examination of new technologies in cervical-cancer screening must also be done as HPVprophylactic vaccines are going to be implemented in different developed countries amongst girls. Professor Hausen’s discoveries in 1984s includes detection of novel human papilloma virus types 16 &18, isolation of the virus types 16(60% cervical SCC1) and 18(10% cervical adenocarcinoma1) genomes, expression of specific papilloma virus DNA genes integrated into the tumour host cell genome & identification and molecular cloning of the HPV16 and HPV18 genomes along with E6 and E7 viral genes proteins expressions in cervical cancer cells by applying nucleic acid in situ hybridization technique(ISH), DNA cloning, DNA probe, from nasopharyngeal carcinoma(Nature. 1970;228(5276):1056-8.), laryngeal cancer,( J Virol. 1982;44(1):393-400),from genital warts (Int J Cancer.1974;13(5):650-6)., penile & vulvar cancer and 60%of cervical cancer cases(Curr Top Microbiol Immunol. 1977;78:1-30). These findings have led to an understanding pathogenesis of cervical cancer1, a characterization of the natural history of the human papilloma virus infection, and paved the way for the development of a preventive vaccine “Gradsil [$ 360 for 3 doses of immunization1]”. But whether these vaccines are really effective in preventing only CIN cervical lesions but also cervical cancer and related deaths? Gradsi; has many vaccine related adverse reactions reported.[Gradsil resulted four deaths, three cases of G.B syndromes, related to immunization and 1637 adverse reaction reported by FDA1] In an Australian study 35 girl of 12 years was given HPV vaccine and of them 23 experienced hypersensitive reactions(9%), 13(5.25%) experienced Urtecaria and severe angioedema. Median time of reaction was 90 minutes2 .we must await the collection of further epidemiological data during coming decades. There remains also fear among guardians of young girls for this vaccine administration. In addition, duration of this vaccine’s protection is unclear: do they provide life-long immunity or will booster doses be needed has not yet been decided1 There remains further health policy related questions 1) Should the vaccine be implemented in National immunization policy in LDC countries where incidence of cervical carcinoma is very high?, .It has been however accepted as National immunization programme for 12-13 years old girl by Gradsil in UK from 2009. 2) Gradsil protects 16 and 18HPV plus two non oncogenic types HPV that can cause genital warts. 3) what should be age of vaccination and its cost effectiveness. Cost effectiveness will depend on duration of vaccine immunity lasting[ targeting initial catch up efforts to women of 18-21 years would be more cost effective what I think ]. 4) Will HPV vaccination to be directed towards male boys also? Presently one of my post graduate students in MD pathology is working with HPV 16 in cervical cancer by ISH, in West Bengal, India and found 90% positive in Saquamous cell Cervical cancers of low socioeconomic group women. The primary screening test with ISH for HPV DNA types in cervical tissues or in vaginal cytology smears is really very costly, requires specially trained personnel and sophisticated laboratory infrastructure. We probably need a new HPV test in primary screening for HGSIL.

    References
    1) Professor pranab Kumar Bhattacharya, Rupak Bhattacharya, Ritwik Bhattacharya, Upasana Bhattacharya etal “Hope a successful candidate inexpensive HPV vaccine will require further 20-25 years to develop for developing countries” Comments on “Effects of Qudrivallent Human Papilloma virus vaccination” -The Lancet vol 370; N 9592; 22nd sept; 2007; P-1031-32
    2) Lew Woek Kap, Nigel Crawford, Mini LK Tang “ hypersensitive reactions to HPV vaccine in Australian School girls- a retrospective cohort study’ BMJ 2008;337;22642;1392


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