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Risk after cervical cancer treatment

Monday 29 October 2007

“Women who have been treated for early signs of cervical cancer have a high risk of the disease decades later,” reported the BBC . According to the report, women who have already had treatment for the most severe grade of pre-cancerous lesions (CIN3), have an increased risk of developing invasive forms of cervical cancer and vaginal cancer 25 years later.

The Guardian , which also covered the story, said “Although their risk decreased with time, those treated for pre-cancerous lesions were still around twice as likely to get cervical cancer than those who had never needed any treatment.”

The reports were based on a large Swedish study that used the data from 130,000  women registered as having abnormal cervical smears treated between 1958 and 2002.

The study is reliable and reinforces the need for the continued surveillance of women who have had treatment for this condition. At present, women in the UK are screened annually for 10 years following treatment. This study is new in that it suggests increased periods of observation for up to 25 years after treatment.

It highlights the increased risk of vaginal cancer, implying that follow up surveillance may be needed for women even if their cervix has been removed during treatment. One implication of this study is that women treated for CIN3 should have long-term regular surveillance, even if they are beyond the current upper age limit for routine (normal) cervical screening.

Where did the story come from?

Dr Bjorn Strander and colleagues from the Sahlgren’s academy, University of Gothenburg in Sweden carried out this research. The study was partially financed with a grant from the county of Halland, Sweden and the Gothenburg Medical Society. It was published in the peer-reviewed medical journal The British Medical Journal .

What kind of scientific study was this?

This was a prospective cohort study based on data in the Swedish cancer registry.

The researchers aimed to study the long-term risk of developing invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3 (CIN3) - the most severe pre-cancerous lesions found after a biopsy of the cervix in women with abnormal cervical smears.

They collected the data from over 130,000 women in Sweden with severe dysplasia or cervical carcinoma in situ (together equivalent to CIN3) treated during 1958-2002. The rate of developing cancer for this group was compared with the risk of cancer in the Swedish general female population. Differences in age between the populations were adjusted for (taken into account).

What were the results of the study?

They found that women who had been treated for CIN3 had more than twice the (adjusted) rate of developing cervical cancer  and were up to seven times more likely to develop vaginal cancer than the general female population. Their results suggested that these women’s risk remained elevated for 20 years or more.

They also found that there was an increasing risk of developing cervical cancer if the abnormal cervical smear had been diagnosed in an older woman, with a much higher risk for women aged over 50.

What interpretations did the researchers draw from these results?

The researchers suggest that although the “question on how follow-up should be carried out is not resolved… this study implies that it has been insufficient”. They go on to call for more studies looking at other strategies of long term follow-up, and in the interim claim that women who have been treated for CIN3 should be offered cytological smears at regular intervals, preferably for at least 25 years after diagnosis with CIN3, independent of age.

The researchers suggest that their results may be partly explained by the trend towards more conservative, less extensive treatments over the years, particularly for younger women who wish to retain the ability to have children and therefore choose not to have treatments that destroy the cervix.

What does the NHS Knowledge Service make of this study?

This was a large well-conducted study. The main results are unlikely to be subjected to statistical bias, and therefore we can be confident that the increase in risk demonstrated by this study, reflects the true increase in women treated over this period of time. Several features of this study allow such confidence:

  • It is a very large study with high quality data collected on most of the women treated over a 44 year time span. This makes it possible to reliably look at the data in subgroups according to age and year of birth.  Despite this size there were some age groups and birth cohorts, however, which had understandably very few cases of cervical or vaginal cancer. For example, there were only two cases of cervical and vaginal cancer in the women who were 80 years or older at the time of their original diagnosis.
  • The data on CIN3 diagnoses was collected before the women developed invasive cancer, the benefit of this is that no bias can be introduced by selective reporting of having had CIN3 among women who later developed cervical or vaginal cancer.
  • The objective nature of the recordings taken for a national cancer registry suggest that misinterpretation of the data is unlikely.

The implications of this study on the timing and duration of follow up for CIN3 will, as the authors acknowledge, need further consideration.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Scientists find new cancer risk.

The Guardian, 27 October 2007

Pre-cancer lesions 'remain risk'.

BBC News, 27 October 2007

Links to the science

Strander B, Andersson-Ellström A, Milsom I, Sparén P.

Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study.

BMJ 2007; October 24 [Epub ahead of print]