Evidence for the presence of high risk human papillomavirus in retinoblastoma tissue from nonfamilial retinoblastoma in developing countries

Retinoblastoma (RB) is a common intraocular tumor of child-hood arising in the retina and accounts for around 3% of thecancers occurring in children below 15 years [1]. The estimatedglobal annual incidence is approximately four per million childrenunder 15 years of age. RB usually presents before the age of2 years and 95% of cases are diagnosed before the age of 5 years.Approximately 40% of RB cases are due to germ line mutationswhile 60% are sporadic in nature. The genetic locus responsiblefor a predisposition to the development RB is located within theq14 band region of chromosome 13.Increased incidence of sporadic RB is seen in less affluentareas of the world such as Latin America, Africa, and Asia(including India) [2,3] suggesting that environmental factors as-sociated with low socioeconomic status may play a role in etio-pathogenesis of RB. The geographic variation observed in RBmay be due to maternal exposure to viral infections or otherenvironmental factors which could cause mutations in utero. Hu-man papillomavirus (HPV) infection is seen more frequently inpregnant than nonpregnant women [4]. An overlap is seen in theepidemiological risk factors for development of RB and HPVinfection. These include smoking, dietary supplements, poor gen-ital hygiene, multiple pregnancies, multiple sexual partners, andsexual intercourse at an early age [5]. This indicates that increasedincidence of RB has been observed in countries with a highincidence of cervical carcinoma [5].Despite the high incidence of RB in India, familial RB is rareand is noted in only 1.7% of cases and majority of patients havenonfamilial or sporadic RB [6].HPV induces posttranslational interactions of its oncoproteinsviz. E6 and E7 with cell cycle regulatory proteins. E6 binds to thetumor suppressor p53 and promotes its degradation via the pro-teosome /ubiquitin pathway. E7 binds to the tumor suppressor Rbproteins pRb, p107, p130, cyclin A, and cyclin E as well as cyclindependent kinases [7]. Binding of E7 to the pRb blocks its activityrendering the proteins inactive.These epidemiological and molecular studies suggest thatHPV may play a role in the development of sporadic RB. Severalstudies have shown a link between HPV infection and RB [5,8–13]. The aims of this study were to determine the presence ofHPV in sporadic RB and to elicit the effects of HPV infection onthe cell cycle regulatory pathway focusing on the pRb family ofproteins.