Two Studies Confirm the Findings of the Cartwright Inquiry

CERVICAL CANCER STUDIES: the legacy of the unethical research at National Women’s Hospital

Research in two papers authored by a team of medical experts at Otago University have vindicated the findings of Dame Silvia Cartwright in her report on the Inquiry into allegations concerning the treatment of cervical cancer at National Women’s Hospital.

The first, reported in the Lancet Oncology in April 2008¹ revealed that between 31 and 50% of women with untreated cervical intraepithelial neoplasia 3 (CIN3), a precancerous disease of the cervix, will develop cervical or vaginal cancer over 30 years.

The study’s results are based on an independent analysis of a clinical study of the natural history of CIN3 carried out by Dr Herbert Green at National Women’s Hospital during the 1960s and 1970s. The team, led by Dr Margaret McCredie, analysed the data compiled by Dr Green and confirmed that there is a high risk of cervical cancer in women not treated after finding precursor lesions, and a very low risk in women who received conventional treatment.

Dr Green’s clinical study was the subject of the judicial inquiry in 1987 now known as the Cartwright Inquiry. The Inquiry found 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 their concerns. One of Judge Silvia Cartwright’s recommendations was that the material should be made available for research.

The records of 1229 women were analysed and it was found that among the 143 women who received only a diagnostic punch or wedge biopsy, 31% 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% developed cervical cancer after 30 years. These estimates took into account later treatments for many of the women.

Among the 593 women who received conventional treatment – usually by a cone biopsy or a hysterectomy – and treatment for recurrent abnormalities, the risk of invasive cancer was about 1% over the same period.

This latest study extends the 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, said “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.”

An article that appeared in the NZ Herald referred to Dr Green’s study as one of the most vilified pieces of research in New Zealand.

The authors of 2008 wrote that “This study provides the most valid direct estimates yet available of the rate of progression from CIN3 to invasive cancer. Women with untreated CIN3 are at high risk of cervical cancer, whereas the risk is very low in women treated conventionally throughout.”

The second paper, published in the Australian and New Zealand Journal of Obstetrics and Gynaecology² confirms that women had curative treatment withheld from them in the course of Dr Herbert Green’s research at National Women’s Hospital in the 1960s and 1970s, thus substantially increasing their risk of cancer.

The study was supported by funding from the Cancer Society of New Zealand and was led by researchers Margaret McCredie and Charlotte Paul from Otago University and Ron Jones from National Women’s Hospital. It confirmed that many women attending National Women’s Hospital with cervical intraepithelian neoplasia 3 (CIN3) were not treated curatively in Herbert Green’s clinical study of the natural history of the pre-cancerous condition and that the women “underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased.”

First study of effects on women

The researchers state “while analyses of the ethical failures of the clinical study have been influential in improving processes for the proper conduct of research, and a number of independent studies have been published using the data, no account has been given previously of the direct effects on the women who participated.”

This study compared the results for women in Dr Green’s 1965-74 “clinical study” with those for women attending the hospital during the years before and after the study. It also compares the women in Green’s study who were initially managed with a small, diagnostic punch or wedge biopsy of the cervix, with patients treated at the outset with procedures such as cone biopsy or hysterectomy intended to cure the women of CIN3.

Examination of medical records

The researchers described how their reanalysis of the women’s medical records and examination of histopathology slides and cytology smears along with “excellent retrieval of material stored for up to 40 years” provided them with the means to obtain an objective and systematic account of the medical experience of the women who were part of Green’s unfortunate experiment. The study also confined the inclusion of the clinical management of each woman to the 10 years following the initial diagnosis, “so that the analysis was not influenced either by the longer follow-up for women in earlier diagnostic periods or by the review and recall of women following the judicial inquiry.” This meant that the total number of medical interventions for each woman was much higher than that documented in the study.

The study revealed that “the risk of invasive cancer of the cervix or vaginal vault was significantly higher among women diagnosed with CIN3 in 1965 – 1974, even though women diagnosed in the earlier period (1955 – 1964) were chiefly an unscreened population, and therefore their disease is likely to have been present for a longer period prior to diagnosis.”

Incidence of cancer much greater

It also found that among women diagnosed with CIN3 in 1965 – 1974, the incidence of invasive cancer was ten times greater in the core group of women who received only a punch or wedge biopsy initially than in women who were treated with the intent to cure their disease. Nearly all cancer deaths among women diagnosed in this period occurred in the core group of women.

The final paragraph of this paper acknowledges the women who were the focus of the Cartwright Inquiry with the words:

“The consequences of the clinical study were profound for the women who participated. When initial treatment of curative intent was withheld, their lives were seriously disrupted by the need to attend hospital for numerous additional medical interventions that would not have been necessary had treatment of curative intent been offered at the outset. Moreover, they had a substantially increased incidence of invasive cancer, with all the emotional stress and physical symptoms that the diagnosis of genital malignancy entails. We have published these findings to document and to acknowledge the harm suffered by these women.”

1. Margaret R E McCredie, Katrina J Sharples, Charlotte Paul, Judith Baranyai, Gabriele Medley, Ronald W Jones, David C G Skegg. 2008: Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncology, 2008 May;9(5):425-34.

2. Margaret R E McCredie, Charlotte Paul, Katrina J Sharples, Judith Baranyai, Gabriele Medley, David C G Skegg, Ronald W Jones. 2010:  Consequences in women of participating in a study of the natural history of cervical intraepithelial neoplasia 3, Australian and New Zealand Journal of Obstetrics and Gynaecology, 2010 Aug;50(4):363-70.