Recurrence of cervical cancer and its resistance to progestin therapy in a mouse model

Studies using K14E6/K14E7 transgenic mice expressing E6 and E7 oncoprotein of human papillomavirus type 16 (HPV16) have demonstrated that estrogen (E(2)) is required for the genesis and growth of cervical cancer. Our prior study using the same mouse model has showed that progestin drug medroxyprogesterone acetate (MPA) promotes regression of primary cervical cancer. In the present study, we use the same transgenic mouse model to determine whether the cancer recurs after MPA therapy. Cervical cancer recurred even if MPA treatment was continued. Unlike primary cervical cancer, the cancer recurred even in the absence of exogenous E(2) when MPA treatment was ceased. Furthermore, recurrent cervical cancer did not fully regress upon MPA treatment. Our results support that MPA fails to completely eliminate primary cervical cancer cells and that remaining cancer cells grow independent of exogenous E(2) and are refractory to MPA.