How little is known about cervical cancer in pregnancy?

L. Sadler1,* and P. Sykes2

1 Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland 2 Department of Obstetrics and Gynaecology, University of Otago, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand

* ; Email: l.sadler{at}auckland.ac.nz

Cervical cancer is widely quoted to be the commonest malignancy in pregnancy. However the epidemiology of both cervical cancer and pregnancy are changing. In most western countries with organised screening the incidence of cervical cancer has dropped dramatically in the last 20 years. There has also been a significant stage shift to earlier stage disease. For many women of childbearing age the diagnosis represents microinvasive cancer. This is associated with an excellent prognosis and can be managed without major impact on current or future pregnancy [1Go]. Coincident with the change in cervical cancer incidence, the mean age at child birth in most western countries has increased to over 30, and increasing age is associated with increasing frequency of many cancers. A study linking California Cancer Registry data with maternal hospital discharge records for 1991–1999 reported a diagnosis of malignancy in association with 1/1000 obstetric deliveries. Breast and thyroid cancers were more common than cervix [2Go]. Clearly the situation is likely to be different in developing countries.

In this issue Germann et al. [3Go] describe a series of 21 cases of cervical cancer managed during pregnancy or the postpartum period. They point out that, despite numerous publications, questions remain regarding cervical cancer in pregnancy. What is the impact of pregnancy on the stage at diagnosis? Does pregnancy adversely affect prognosis? What is the consequence of planned delay of treatment so the pregnancy can be continued to a viable gestation? What is the most appropriate treatment?

Regarding stage at diagnosis, it is noted that in this study microinvasive disease is excluded, and yet still 71% were stage I. 76% were asymptomatic but it is not reported how many cases were diagnosed by smear. Pregnancy offers an opportunity for cervical screening but also brings challenges for early diagnosis. Colposcopy is technically more difficult, the complication rate following biopsy is higher, and further, vaginal bleeding caused by cervical cancer may go undiagnosed due to assumptions about pregnancy related causes. However, although some women may have a delayed diagnosis in pregnancy, the data in this paper and previous reports would generally suggest that stage is not affected adversely by pregnancy and may even be improved [4Go].

Regarding prognosis, the outcome by stage of women in the series of Germann et al. is good [3Go]. However the study was not designed to compare survival with non-pregnant women. Since 1990, three studies have compared survival of cases with controls matched for age, year of diagnosis, stage, and in two studies also for treatment modality and histological type [4Go–6Go]. These studies compared in total 161 cases and 216 controls. No study found a difference in survival, although one found women diagnosed postpartum fared worse than controls or women diagnosed antepartum. The data are limited, but do not show that the prognosis of cervical cancer is adversely altered by pregnancy.

Germann et al. [3Go] suggest that treatment of cervical cancer is reasonably delayed for women diagnosed in late second or third trimester (i.e. after 20 weeks). It is common practice to allow a 6-week delay to definitive surgery if it is not performed within 72 hours of a diagnostic cone biopsy [7Go]. With recent improvements in neonatal care, the delay to allow fetal maturity has shortened, and it may be reasonable to consider lowering the gestation at which termination of pregnancy is classically recommended to expedite curative treatment.

Germann et al. [3] also conclude that treatment of stage 1b cancers less than 2 cm without lymph node metastases diagnosed in first trimester may ‘reasonably’ be delayed until fetal viability. We would concur as these lesions have an excellent prognosis and treatment delay is unlikely to be associated with a poor outcome. However, the data reported in the literature are extremely limited, as shown in Table 1, which lists survival outcome following treatment delay of at least 6 weeks among 49 cases of stage 1b or greater cervical cancers published since 1980. Of these 49 cases, 47 were recorded to be alive without recurrence. However, only nine of these cases, including the five reported by Germann et al. were diagnosed in first trimester.


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Table 1. Summary of cases published since 1980, with maternal outcome data, where treatment delay of at least 6 weeks in pregnancy has been described among women with 1b+ cervical cancer

 
Adequate data are unlikely from any single series of pregnant women, although the data need not be limited to pregnant women as the effect of delay is independent of pregnancy (assuming prognosis is unchanged in pregnancy). An ideal study would compare the survival of women with a delay to treatment, matched by age, year of diagnosis, stage, histological type, with women who did not have delay to treatment. To assess a reduction in survival from 90% to 80% would require 200 women in each group with 80% power and 95% confidence.

Regarding treatment options, the treatment modalities delivered for the patients described in this issue appear to have provided safe and effective management. This largely reflects a considered approach to standard management options currently used in gynaecological oncology centres. Recent developments have seen improved imaging techniques and evidence of improved survival following treatment with chemoradiation. The use of conservative surgical techniques has offered women the opportunity of future pregnancies. Neoadjuvant chemotherapy prior to definitive surgical management has been advocated by some authors and there are case reports of the use of chemotherapy in pregnancy delaying the need for immediate surgery [8Go–10Go]. Due to the rarity of cervical cancer in pregnancy it is almost impossible to anticipate adequate data to define the optimal management for individual women.

In summary, cervical cancer remains an important but rare condition in pregnancy. The key to further limitation of mortality and morbidity from this condition is cervical screening. However, cases will still occur. Current data suggest that pregnancy does not adversely affect stage at diagnosis or prognosis. However, even with the further cases added in this issue, there are inadequate data to advise women from an evidence base on whether delay of treatment to facilitate delivery is safe, and there are almost no data upon which to base advice to women with disease beyond stage 1b. Treatment should be multidisciplinary and individualised following careful counseling. Further understanding of the natural history of cervical cancer is required. The collaborative collection of data relating to treatment and outcome, as advocated by the authors, is strongly encouraged.

References

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