Table 3.

Key hypotheses describing the origin of ovarian cancer

Hypotheses	Main features	Key citations
Tubal hypothesis	OSE is not embryologically derived from Mullerian ducts, however ovarian neoplasms present Mullerian features. This suggests that OC originates from the epithelium of the fallopian tube where p53 signatures have been observed and the disease later migrates onto the ovarian surface.	35, 27, 86, 89, 142
Inflammation hypothesis	Prolonged and sustained inflammation in the ovary gives rise to neoplastic changes. Ovulation is an inflammatory process. The OSE is also exposed to the peritoneal cavity and therefore is exposed to environmental and xenobiotic stress.	4, 13, 55
Gonadotropin hypothesis	Factors that induce gonadotropin release from the pituitary (such as loss of negative feedback by estrogens to the pituitary) induce ovarian carcinogenesis.	19, 21, 105, 107, 118, 167
Incessant Ovulation hypothesis	Continuous ovulation and consequential rapid wound healing of the OSE results in an immense inflammatory burden on the ovaries and can trigger oncogenic changes. Ovarian cancer incidence can also be positively correlated with the number of ovulations. This hypothesis combines elements of both the inflammation and gonadotropin hypotheses.	34, 51, 52, 111, 126