Human papillomavirus 16 and 18 expression in conjunctival intraepithelial neoplasia.
OBJECTIVE
To evaluate conjunctival intraepithelial neoplasia (CIN) and normal conjunctiva for the presence of human papillomavirus (HPV) DNA and for expression (as detected by the presence of mRNA) of the HPV E6 region.


METHODS
Prospective, case-controlled study.


METHODS
Ten consecutive patients who underwent CIN excision by one surgeon (CLK) and five age-matched control subjects who underwent retinal detachment repair at the Bascom Palmer Eye Institute.


METHODS
A reverse transcriptase in situ polymerase chain reaction (PCR) technique was used to search for the presence of HPV mRNA in CIN specimens from 10 consecutive patients who underwent CIN excision by one surgeon (CLK) at Bascom Palmer Eye Institute, as well as in clinically uninvolved conjunctival specimens from the same eyes of these patients. In addition, conjunctival specimens from five control subjects (age-matched to five of the cases), who had no clinically identifiable conjunctival disease and who underwent retinal detachment repair at the Bascom Palmer Eye Institute, were analyzed in a similar manner. The clinical diagnoses of CIN and normal conjunctiva were confirmed histopathologically in all cases by an ocular pathologist, who was masked as to the patients' clinical diagnoses, and the PCR testing was performed by an investigator (GJN) who was masked as to the clinical diagnoses.


RESULTS
HPV 16 DNA and mRNA were present in five CIN specimens, and HPV 18 DNA and mRNA were present in the other five CIN specimens; neither HPV 16 or 18 DNA nor mRNA were detected in any of the control specimens or in any of the clinically uninvolved conjunctival specimens (P < 0.001). In each of the CIN specimens, 20% to 40% of the dysplastic cells expressed the HPV E6 region.


CONCLUSIONS
HPV 16 or 18 DNA and mRNA corresponding to the E6 region were detected in all CIN specimens examined. HPV 16 or 18 DNA or mRNA was not present in any of the control or uninvolved conjunctival specimens. The consistency of the current findings with those reported for human cervical malignant lesions, and the fact that the protein encoded by the E6 region of HPV 16 and 18 has been shown to form a complex with the protein encoded by the host tumor suppressor gene p53, provide strong evidence for an etiologic role of HPV in the development of CIN.
Scott
Ingrid U
IU
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL 33101, USA.
Karp
Carol L
CL
Nuovo
Gerard J
GJ
D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D003230:Conjunctival Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins