Point-of-Care, Real-Time Optical Imaging to Enable Screening for Cervical Cancer and Its Precursors in Low-Resource Settings

A new mobile diagnostic and treatment unit is being developed by BCH to address the loss-to follow-up associated with the mobile screening program and demonstrate POC diagnosis by HRME. The mobile diagnostic and treatment unit will be equipped with the tools and infrastructure necessary to perform HRME, VIA, colposcopy, biopsy and treatment with cryotherapy. A team of a colposcopist, nurse, nursing assistant, and driver will staff the mobile diagnostic and treatment unit. The unit will travel to offer follow-up diagnostic and treatment services to women who have screened positive during a prior visit with the mobile screening unit. The mobile diagnostic and treatment unit will be constructed and maintained at BCH.

The study will include 200 women with abnormal Pap tests identified through BCH's existing mobile screening program. Participants will be randomized by cluster to receive follow up care either through the new mobile diagnostic and treatment unit (experimental arm) or through recall to BCH (standard of care). We are using cluster randomization to avoid contamination between arms because some women getting mobile unit services may be concerned that they are getting lesser services than what they could get at BCH or some women being referred to BCH may resent not having the convenience of a mobile unit. Because the areas visited by the mobile units are geographically isolated, we do not anticipate any patients crossing over to the other study arm.

VIA will be performed with 5% acetic acid applied to the cervix and any abnormal lesions noted. Standard colposcopy will then be performed and abnormal lesions noted. Proflavine (0.01%) will then be applied topically. Lugol's solution will then be applied and colposcopy performed and abnormal lesions noted. Proflavine (0.01% will then be reapplied. HRME images will be acquired from any areas that are abnormal by VIA and/or colposcopy. In addition, all 4 quadrants will be probed by HRME (4Q HRME) to ensure that non-acetowhite lesions are also located. The provider will note their impression of the lesion and the HRME image at each site (normal, benign, low-grade precancer, high grade precancer or cancer). The entire HRME imaging procedure should add less than 10 minutes to the standard colposcopy exam. VIA, colposcopy and HRME observations will recorded by quadrant. Any abnormal areas by VIA and/or colposcopy will be biopsied. If no abnormal areas are noted, one cervical biopsy will be obtained from a normal appearing area with a HRME image of this area obtained. Two expert pathologists, blinded to all study results, will review histology and classify as either normal, CIN1, CIN2, CIN3, AIS or cancer, according to standard criteria; discrepant results will be resolved by consensus review.

TREATMENT:

Women randomized to the mobile diagnostic and treatment unit who have a HSIL Pap and/or a lesion noted by VIA and/or colposcopy will undergo immediate treatment with cryotherapy following biopsies, provided the lesion meets the following criteria: 1) covers <75% of the ectocervix; 2) can be fully covered with the cryotherapy tip; 3) does not extend into the endocervical canal. If the colposcopic findings are concerning for invasive cancer or the lesion is not amenable to treatment with cryotherapy, the patient will be referred immediately to BCH for additional evaluation and treatment per standard of care.