Contraceptive drug helps protect against cervical cancer
Researchers from the University of Houston have reported that medroxyprogesterone acetate (MPA), the active ingredient in the common contraceptive injection Depo-Provera, can prevent the development of cervical cancer in mice with precancerous lesions. The drug also decreased existing precancerous lesions.
Cervical cancer is the third most common and third most deadly cancer in women worldwide. Human papillomavirus (HPV) is considered a major factor in the development of cervical precancerous lesions and cancers — but although HPV vaccines are effective at preventing HPV infections, they may not be readily available to women in underdeveloped countries and those of low socioeconomic status. And while surgical removal of precancerous lesions (cervical intraepithelial neoplasia or CIN) can be clinically beneficial, adverse effects include shortening the cervix and increasing the risk of complications in future pregnancies.
“Although HPV vaccines have been available since 2006, the incidence of precancerous lesions … and cervical cancer due to HPV has not decreased substantially,” said lead investigator Dr Sang-Hyuk Chung. “The high cost and lack of a global vaccination program have limited the use of these vaccines. A non-invasive, efficient means to treat CIN is urgently needed.”
Similar to cervical cancer progression in women, mouse cervical neoplastic disease develops through multiple stages, starting from CIN and culminating in invasive cancer. Dr Chung and co-investigators had previously shown that MPA regresses cervical cancer in a mouse model expressing HPV genes responsible for cancer; in their latest study, they treated CIN-bearing mice with MPA.
The investigators found that cervical cancer did not develop in mice receiving MPA. Further, CIN was absent in most MPA-treated mice, indicating that MPA may be chemoprotective — not only preventing CIN from progressing to invasive cancer, but also promoting its regression. The study thus determined that MPA inhibited cell proliferation and promoted apoptosis (cell death) in CIN lesions. In addition, the preventative effect of MPA was absent in HPV transgenic mice in which the expression of progesterone receptor (PR) was genetically prevented.
These results, published in The American Journal of Pathology, suggest that MPA is efficient for treating PR-positive CIN lesions. PR positivity may be a useful biomarker for selecting patients who may benefit from MPA in future clinical trials.
“We are optimistic because the mouse model we used in this study has been validated and revealed important mechanisms of cervical cancer,” Dr Chung said. “MPA-injectable suspensions are cheap and stable at room temperature; therefore, there is no need for special storage, which facilitates easy distribution.
“It is already used as the self-injectable contraceptive Depo-Provera, and thus translation into clinical use would be faster. MPA would be an effective chemoprevention agent for cervical cancer, particularly in women who do not have access to HPV vaccines. However, we should note that several studies have shown that MPA increases the risk of breast cancer.”
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