AimTo develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.MethodsCervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.ResultsThe overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.ConclusionThe subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model.

Cancer research has long relied on animal models for the study of disease mechanisms and new therapeutics. Future cancer treatments are likely to rely heavily on patient-derived xenograft models to develop novel treatments and tailor regimens to individual patient needs. However, specific models for cervical cancer and cervical dysplasia are limited. Only 3 models have been described in the published literature. A transgenic model for cervical cancer has allowed for the study of the differential contributions of the human papillomavirus 16 proteins E6 and E7 during oncogenesis. This model has also shown dysplasia development, although this has received little attention. A patient-derived tumor xenograft model where cervical cancer tissue is transplanted to the subcutaneous and orthotopic sites has been described. Here we review the reported transgenic and xenograft models, their strengths and limitations, and highlight the potential for the development of improved models to study cervical neoplasia.

Both medical and midwifery students demonstrated a significant improvement in their test scores and for most students the examination process itself was a positive learning experience.