Elsevier

The Lancet Oncology

Volume 4, Issue 11, November 2003, Pages 670-678
The Lancet Oncology

Review
Epidemiology and aetiology of gestational trophoblastic diseases

https://doi.org/10.1016/S1470-2045(03)01245-2Get rights and content

Summary

Gestational trophoblastic diseases (GTD) consist of a group of neoplastic disorders arising from placental trophoblastic tissue after normal or abnormal fertilisation. The WHO classification of GTD includes hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour, and miscellaneous and unclassified trophoblastic lesions. GTD have a varying potential for local invasion and metastases and they generally respond to chemotherapy. Broad variations in the distribution of GTD exist worldwide, with higher frequencies in some parts of Asia, the Middle East and Africa, but the extent to which they can be attributed to methodological difficulties in obtaining accurate rates is unclear. Maternal age and a history of GTD have been established as strong risk factors for hydatidiform mole and choriocarcinoma. We review published data on the worldwide distribution of GTD, original data from cancer-registry-based statistics on choriocarcinoma, and major aetiological hypotheses, including parental age, AB0 blood groups, history of GTD, reproductive factors, oral contraceptive use, and other environmental factors.

Section snippets

Hydatidiform mole

Trophoblasts are specialised epithelial cells, derived from the outermost layer of the blastocyst that originates in early embryonic differentiation. On the basis of morphological, immunophenotypical, and functional studies, trophoblasts can be classified into three distinct populations: cytotrophoblasts, syncytiotrophoblasts, and intermediate trophoblasts. The cytotrophoblasts are the germinative cells situated on the surface of the chorionic villi. In early gestation, cytotrophoblasts

Hospital-based studies and surveys

Table 3 shows the ratios of GTD per 100 000 pregnancies, deliveries, or live births from selected studies. Data from Europe, North America, and Oceania showed intermediate ratios of GTD ranging from 66 per 100 000 pregnancies in Italy8 to 121 in the United States.14, 15 In contrast with the generally low or intermediate ratios found in these regions, a remarkably high ratio was found in Alaska (389 per 100 000 deliveries)11 and Hawaii (460 per 100 000 live births).12 The largest study of these

Parental age

The best established risk factor associated with HM is maternal age.2, 7, 30, 43, 44, 45 Overall, the pattern of risk was similar across all studies and for the different types of GTD, with a higher risk for women under 20 years old (relative risk 1·1–10·0) and for women older than 40 years (3–11) compared with women aged 20–35. Risk estimates were extremely high for women older than 45 years (relative risk 107–841), although estimates were based on a smaller number of cases. Differences in the

Conclusion

CHM and PHM are two different entities. CHM has exclusively a paternal karyotype, generally a homozygous one, whereas PHM is triploid with both maternal and paternal chromosomes. A women with CHM has a substantially increased risk of developing persistent GTD. Whether heterozygous CHMs, arising from dispermy, have a higher risk of progression to choriocarcinoma than their homozygous counterparts is controversial.

In North America and Europe, ratios of HM are about 100 per 100 000 pregnancies.

Search strategy and selection criteria

Data for this review came from published studies selected from more than 7000 citations generated from searches of MEDLINE and ISI Current Contents databases with the search terms “gestational trophoblastic disease”, “hydatidiform mole”, “choriocarcinoma”, and “risk factors”. We also selected references from some papers published in English between 1966 and 2003. For GTD we limited the review to studies published after 1977, which included at least 65 cases. For choriocarcinoma we included all

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