Cervical cancer: New Zealand study provides key evidence

A New Zealand study reported early online in the international journal Lancet Oncology this week has shown that between 31 and 50 per cent of women with untreated CIN3, a pre-cancerous disease of the cervix, will develop cervical or vaginal cancer over 30 years. The study also shows that the likelihood of developing cervical cancer after conventional treatment for pre-invasive disease was about 1 per cent over the same time period. The authors say that the study provides the most valid direct estimates of the rate of progression from CIN3 to invasive cancer. CIN3, cervical intraepithelial neoplasia, is a pre-cancerous condition usually detected by a cervical (or Pap) smear test.

The results are based on an independent analysis of a clinical study of the natural history of CIN3 undertaken at National Women's Hospital in Auckland, in which treatment of curative intent was withheld or delayed for many women who were first diagnosed between 1965 and 1974. The clinical study was subject to a judicial inquiry in 1987 (the Cartwright Inquiry), which concluded that the study was unethical because treatment was withheld without consent, monitoring of outcomes was inadequate, and the study was not ended when clinicians raised concerns. Judge Cartwright recommended that the material should be made available for research.

The current study extended an earlier analysis by Dr Bill McIndoe and colleagues which was published in 1984. Professor Ron Jones, who instigated the current study and was involved in the earlier analysis, commented: "The present study has employed different methods of analysis and the follow-up has been extended to 30 years. However the findings are very similar to those reported by our group 24 years ago. Whereas in the original study we assessed the risk of cancer as 25 times greater in women with inadequately treated CIN3, compared to treated women, the present estimates are even higher."

The findings show the importance of cervical screening because they demonstrate both the very high risk of cervical cancer in women with pre-cancerous disease who are not treated, and the very low risk among women treated adequately initially and then followed up with regular cervical smears and with treatment of any abnormalities that occur.

Among the 143 women (out of the total of 1063) who received only a small diagnostic biopsy (punch or wedge) initially, 31 per cent developed cervical cancer after 30 years. In the subset of 92 women who had persistent disease within 24 months of the original diagnostic biopsy, 50 per cent developed cervical cancer after 30 years. These estimates took into account later treatments for many of the women. The lower proportion in the former group is because of early natural regression of the disease in some women.

Among the 593 women who received conventional treatment (usually cone biopsy or hysterectomy) and treatment for recurrent abnormalities, the risk of invasive cancer was about 1 per cent at 30 years. This subset of women at National Women"s Hospital was under close clinical surveillance, with appropriate treatment of recurrences.

One of the authors, Otago Vice-Chancellor David Skegg, said that the study underlines the value of cervical screening. "There was much controversy surrounding this procedure in the past. We can now start to estimate the thousands of cancers that are being prevented world-wide. Cervical screening is a highly effective measure, so long as women found to have abnormalities are treated adequately and followed up."

Another author, Professor Charlotte Paul, who was a medical advisor to the Cartwright Inquiry, commented that the results confirm that during the period of the clinical study many women were inadequately treated, including 92 women who received no treatment for at least 24 months after diagnosis, despite having evidence of persistent disease. "Over the years some people have rejected the idea that treatment really was withheld from women in the study. Regrettably, our results confirm that treatment was withheld."