Cervical intra-epithelial neoplasia (CIN) is a pre-cancerous lesion of the cervix uteri (neck of the womb) caused by human papillomavirus (HPV), which may develop into cervical cancer, if not treated. Local treatment involves destroying or removing the abnormal area of the cervix, leaving most of the cervix, and the uterus in place maintaining the ability to become pregnant in the future, if desired. Certain types of local treatment may also be suitable for very early cervical cancer (stage IA1) if the tumour is very small and very unlikely to have spread beyond the cervix. There are many studies investigating whether the local treatment for CIN and early cervical cancer increases the risk of preterm birth (PTB) in subsequent pregnancies. However, there is no definite conclusion and this creates confusion for both the medical staff and women who may be recommended treatment, but also want to have children in the future.
The aim of the review
We aimed to assess whether the local conservative treatment techniques for cervical precancer (CIN) and early cervical cancer increased the risk of complications for mother and baby during pregnancy occurring after treatment, and especially whether treatment is associated with an increase in the risk of PTB. We also studied whether the risk of PTB increases with increasing amount of cervical tissue removed.
We included all studies that investigated the effect of treatment of CIN and early cervical cancer on late pregnancy outcomes (beyond 24 weeks of gestation) in women who had been treated previously for CIN and early cervical cancer, as compared to women who had not been treated. We excluded studies that had no untreated comparison group, reported pregnancy outcomes in women who had undergone treatment during pregnancy, or had a high-risk treated, comparison group or both.
What are the main findings?
We included 69 studies (6,357,823 pregnancies: 65,098 pregnancies of treated and 6,292,725 pregnancies of untreated women). Treatment was associated with an increased risk of PTB before 37 pregnancy weeks, as well as an increased risk of severe PTB (less than 32 to 34 pregnancy weeks), extreme PTB (less than 28 to 30 pregnancy weeks) and pPROM (premature preterm rupture of the membranes) as compared to untreated women. The risk of overall PTB was higher for women treated by excisional methods (where tissue is cut away) than by ablative treatments (where tissue is destroyed instead of being cut away). Multiple treatments, as well as increasing amounts of tissue removed at the time of treatment, were associated with an increased risk of overall PTB. However, women with CIN who were not treated also had a higher risk of overall PTB than the general population. Low birth weight (LBW) < 2500g), neonatal intensive care unit (NICU) admission and perinatal mortality rates were also found to be increased after treatment.
What is the quality of the evidence?
Due to the nature of the intervention and outcomes studied, we were only able to include observational studies, of which the majority were retrospective. These types of studies are of low quality with a high level of variability between the studies, therefore the level of evidence for most outcomes can only be considered to be of low or very low quality.
What are the conclusions?
Women with CIN have a higher baseline risk for PTB than the general population and the treatment for CIN probably increase this risk further. The risk for PTB is probably higher when excisional techniques are used than for ablative treatments. Also, the risk of PTB appears to increase with multiple treatments and increasing amounts of tissue removed. However, these results should be interpreted with caution due to the low and very low quality of the included studies.