The ON Saga — The Biological and Clinical Significance of Cervical Intraepithelial Neoplasia *

It has been my great pleasure to have known Eric Mackay for a great many years. What began as a mere acquaintance in prep. school has grown from our residency days at the Royal Women’s Hospital, Melbourne, into a warm and longstanding friendship. This has provided an unique opportunity to witness a most distinguished career. I am delighted to have the opportunity of paying tribute in this valedictory symposium, marking Eric’s retirement from the Foundation Chair of Obstetrics and Gynaecology of the University of Queensland. Other speakers have already elaborated upon his many achievements. However, it was only relatively recently that he undertook a major role as the senior medical advisor to Judge Silvia Cartwright in ‘The Committee of Inquiry into Allegations Concerning the Treatment of Cervical Cancer at the National Women’s Hospital’ in Auckland, New Zealand. This must have been a most time consuming, protracted task involving great disruption to his own personal and professional commitments and requiring the utmost of his diplomatic skills and professional knowledge. His competence and expertise in that enquiry have been widely acknowledged and publicly lauded. The topic which I have been invited to expound upon was indeed the essential core of that enquiry namely, the CIN saga. It is to Schiller that the credit belongs for the original concept that cancer of the cervix might begin as a surface lesion, remaining for a variable and often considerable time before eventually invading the stroma. However, pathologists can still differ in their opinion as to where glandular involvement stops and invasion begins. defined at the Second International Conference in Cytology) required that the full thickness of epithelium be composed of undifferentiated neoplastic cells, whilst the term ‘dysplasia’ designated lesions of atypical epithelium short of the definition of CIS. At the time, there was no unanimity that they were part of the same biological spectrum, there being extreme bodies of opinion, from those who regarded dysplasia as always being benign and never progressing to CIS or invasive cancer to those who regarded CIS, not as a precursor but as an already definitive cancer, albeit confined to the surface epithelium. The term CIN therefore, served to emphasize that dysplasia and CIS were part of the same bioligical spectrum and eliminated the word carcinoma, with its connotation of established malignant disease. In particular, the term CIN 3 combining previously designated severe dysplasia and CIS served to acknowledge the thin dividing line of histological diagnosis and biological behaviour.