Evidence for the presence of high risk human papillomavirus in retinoblastoma tissue from nonfamilial retinoblastoma in developing countries.
BACKGROUND
The prevalence of human papillomavirus (HPV) infection in India is high. HPV infection is known to cause cervical cancer and has also been implicated in the pathogenesis of retinoblastoma (RB), a common intraocular malignant tumor of childhood which can be familial or sporadic. Despite the high incidence of RB in India, its familial form is rare. Hence this study was undertaken to investigate whether high-risk HPV types 16 and 18 are involved in the development of RB.


METHODS
Formalin fixed paraffin embedded RB tissues (n = 76) including prospective cases with corresponding maternal cervical smears (n = 10) were analyzed for the presence of HPV DNA sequences. Expression of the cell cycle regulatory proteins viz; p105, p107, p30, p16, E2F-1, E2F-4, and MiB-1 was studied by immunohistochemistry (IHC) (n = 34).


RESULTS
A total of 53 out of 76 (69.7%) cases were positive for HPV, of these 3 cases were positive for HPV-16, 23 for HPV-18, and 27 for both HPV-16 and -18. Of the prospective cases (n = 10) studied, five cases along with the corresponding maternal cervical cytology smear had identical HPV status. HPV-16 positive tumors were classified as well differentiated (P = 0.013). Nuclear expression of pRB2/p130 showed significant association with HPV-16 infection (P = 0.04) or dual infection of HPV-16/-18 (P = 0.02).


CONCLUSIONS
Our study lends support to the hypothesis that infection of HPV-16/-18 may play an important role in the development of nonfamilial form of RB in children in India.
Department of Pathology, Tata Memorial Centre, Mumbai, India.
Omshree A
OA
Shetty
Kikkeri N
KN
Naresh
Shripad D
SD
Banavali
Tanuja
T
Shet
Rupali
R
Joshi
Sajid
S
Qureshi
Rita
R
Mulherkar
Anita
A
Borges
Sangeeta B
SB
Desai
D015139:Blotting, Southern; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D003906:Developing Countries; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000473:pathology* / Q000821:virology; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012175:Retinoblastoma / Q000453:epidemiology* / Q000473:pathology* / Q000821:virology; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014626:Vaginal Smears
D018797:Cell Cycle Proteins; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D016160:Retinoblastoma Protein