Indian Jou rnal of Expcrimcntal Biolo: Vol. 4 1, August 2003. pp. 789-796 Review Article Genetic alterations in cervical cancer Khalida Wani & C K K Nair* Radiation Biol ogy Di vision. Bhabha Atomic Rcs earch Ccntrc, Mumbai 400085. India In th c pathogc ncsis or ccrvical cancer th e role or hUl11an papillomavirus ( HPV ) infection is wcll cs tabli shcd. However. ot her than HPV in fect ion th e gCIll:t i cs of cervical ca ncc r rcmai ns poorly undcrslOod. In the path oge nes is of cervical can ce r th rec major fa clOrs arc invol ve d. two of which arc related to the prcsencc of H I'\! and thc third is Ihc recurrent genctic al terations not link cd to HPV in fe ctio n. Seve r al chromosomal reg ions with recurrent l oss or heterozygosity ( LOH ) in cervical cancer ha ve been identiried. Howe ve r: Ihe putative tumor suppresso r genes locatcd in th ese chromosoma l l oea li ons arc ye t to be iden ti fi ed. Recurrcnl ampl ifi cations ha ve been mapped to the shorl arm or chromosome 3 in in vasive cancer. Microsatellite instability and mutator phen olype do not pl<l y a major role in cervical ca rci nogenesis. As in o th er cancers. cervical can cer too requires th e accumulalion or gcnctic alterations 1' 01' carcinogencs is 10 occ ur. I dentificatio n or th esc alterations could help to provide a beller understanding or thc disease and thu s impro vc Ireatment. Key word s: Ccrvical ca ncer, Genetic <Jlterations. Human p<lpiloma vi ru s. Loss or hetcozygos ity ( LOH). Millis<llellite instahi lity Cervica l ca ncer represe nt s th e fifth mo st common neoplasm worldwide and is seco nd only to breast ca ncer as a ca use of ca nce r mortality in women I. Ac cording to th e nat ional cancer control program for Indi a, it is th e mo st common gy neco log i ca l ma li gnancy obser ved among Indi an women 2 . The World Health Organization estimat es th at Indi a alone accounts for 18% of the app r ox imately 900, 000 cervical cancer victims each yea r. Introdu c ti on of th e Papa ni co laou (Pap) testing has reduced th e in cidence of cervical cancer cases in developed nations with good sc reeni ng programs. The ri sk of ce rvical cancer in developing nations. however, rema ins hi gh'. World wid e, an estimated 900 000 women are di ag nosed with thi s malignancy each year. Three quaIters of a ll th e cervical cancers in th e world occ ur in developing cou ntri es a nd over 90, 000 occ ur in Indi a alone. Associated mOl1ality is exceeded onl y by th at of brea st cancer. In countries such as Nigeria, Liberia and Algeria cervica l cancer represe nt s about 30% of a ll female mali gnancies. The rate increas es upt o 50% in Indi a 4 and Korea. Co untri cs with low rat es of this disease include Israe l, Ku wa it , Spain and Irela nd ). De spite the considerable effol1 and cos tl y health care reso urces expended on women with abno rm al pa p smears, th e total contribution of ce rvical neopl as ia to cancer relat ed mOl1ality may be th e largest of any neoplas ti c process a nd thus st ill conti nu es to present a *Corr espondent author : Phon c: +9 1-022-25593869 Fa x: +9 1-022 -2 5505151 Emai l: ck nai r@magnulTl .barc .ern eLin significant challenge to th e hea lth care co mmunity. Acco rdin g to the national cancer control program for India, cervical cancer is the most common maligna nc y affecting wo men accounting for nearly 50% of a ll fe male ma li g nan cies 6 . According to th e data avai l ab le from pop ul ation based cancer regi st ri es at Bangal or e, Mumbai , and Madra s, the crude in c id ence rates are at 39.7 , 15 .4 a nd 46.5 per 100 000 fema l es respecti ve l /. The data from th e popul at ion based cancer registr y functioning in Ko lk ata from 1997 reveals that of th e 8028 cancer cases in females , 1537 were of ca ncers of the ut e rin e cerv i x. Cervi ca l cancer, thu s, is a major public health problem in Indi a, s in ce not on ly is th e in cidence hi gh, but 70% of the cases prese nt with advanced stage of th e disease S.'). Cervical neoplasia Consiste nt with an ori g in in the transformation zo n e, most cervical cancers are sq uamous ce ll carc in omas, with adenocarcinomas and mix ed adenosquamous tumors acco unting fo r mo st of the remainde r. Other hi stologi ca l types such as melanomas, sarcomas, and metas tati c tumors are ve ry rare. Squamous carc in omas of th e ce rvix res ult from th e progressio n of prein vas ive prec urso r lesions ca ll ed "cervical intraep it hel ial neoplasia (CIN)". Multistep pathogenesis of cervical cancer A hypo th et ical sc heme describing th e multi step pathogenes is of cervical cancer is presented in Fig. I.