Redesign of a rapid, low-cost HPV typing assay to support risk-based cervical screening and management.

Accelerated cervical cancer control will require widespread human papillomavirus (HPV) vaccination and screening. For screening, sensitive HPV testing with an option of self-collection is increasingly desirable. HPV typing predicts risk of precancer/cancer, which could be useful in management, but most current typing assays are expensive and/or complicated. An existing 15-type isothermal amplification assay (AmpFire, Atila Biosystems, USA) was redesigned as a 13-type assay (ScreenFire) for public health use. The redesigned assay groups HPV types into four channels with differential cervical cancer risk: (a) HPV16, (b) HPV18/45, (c) HPV31/33/35/52/58 and (d) HPV39/51/56/59/68. Since the assay will be most useful in resource-limited settings, we chose a stratified random sample of 453 provider-collected samples from a population-based screening study in rural Nigeria that had been initially tested with MY09-MY11-based PCR with oligonucleotide hybridization genotyping. Frozen residual specimens were masked and retested at Atila Biosystems. Agreement on positivity between ScreenFire and prior PCR testing was very high for each of the channels. When we simulated intended use, that is, a hierarchical result in order of clinical importance of the type groups (HPV16 > 18/45 > 31/33/35/52/58 > 39/51/56/59/68), the weighted kappa for ScreenFire vs PCR was 0.90 (95% CI: 0.86-0.93). The ScreenFire assay is mobile, relatively simple, rapid (results within 20-60 minutes) and agrees well with reference testing particularly for the HPV types of greatest carcinogenic risk. If confirmed, ScreenFire or similar isothermal amplification assays could be useful as part of risk-based screening and management.

A Deep Clustering Method For Analyzing Uterine Cervix Images Across Imaging Devices.

Visual inspection of the cervix with acetic acid (VIA), though error prone, has long been used for screening women and to guide management for cervical cancer. The automated visual evaluation (AVE) technique, in which deep learning is used to predict precancer based on a digital image of the acetowhitened cervix, has demonstrated its promise as a low-cost method to improve on human performance. However, there are several challenges in moving AVE beyond proof-of-concept and deploying it as a practical adjunct tool in visual screening. One of them is making AVE robust across images captured using different devices. We propose a new deep learning based clustering approach to investigate whether the images taken by three different devices (a common smartphone, a custom smartphone-based handheld device for cervical imaging, and a clinical colposcope equipped with SLR digital camera-based imaging capability) can be well distinguished from each other with respect to the visual appearance/content within their cervix regions. We argue that disparity in visual appearance of a cervix across devices could be a significant confounding factor in training and generalizing AVE performance. Our method consists of four components: cervix region detection, feature extraction, feature encoding, and clustering. Multiple experiments are conducted to demonstrate the effectiveness of each component and compare alternative methods in each component. Our proposed method achieves high clustering accuracy (97%) and significantly outperforms several representative deep clustering methods on our dataset. The high clustering performance indicates the images taken from these three devices are different with respect to visual appearance. Our results and analysis establish a need for developing a method that minimizes such variance among the images acquired from different devices. It also recognizes the need for large number of training images from different sources for robust device-independent AVE performance worldwide.

Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage.

BACKGROUND: Accelerated global control of cervical cancer would require primary prevention with human papillomavirus (HPV) vaccination in addition to novel screening program strategies that are simple, inexpensive, and effective. We present the feasibility and outcome of a community-based HPV self-sampled screening program. METHODS: In Ile Ife, Nigeria, 9406 women aged 30-49 years collected vaginal self-samples, which were tested for HPV in the local study laboratory using Hybrid Capture-2 (HC2) (Qiagen). HPV-positive women were referred to the colposcopy clinic. Gynecologist colposcopic impression dictated immediate management; biopsies were taken when definite acetowhitening was present to produce a histopathologic reference standard of precancer (and to determine final clinical management). Retrospective linkage to the medical records identified 442 of 9406 women living with HIV (WLWH). RESULTS: With self-sampling, it was possible to screen more than 100 women per day per clinic. Following an audio-visual presentation and in-person instructions, overall acceptability of self-sampling was very high (81.2% women preferring self-sampling over clinician collection). HPV positivity was found in 17.3% of women. Intensive follow-up contributed to 85.9% attendance at the colposcopy clinic. Of those referred, 8.2% were initially treated with thermal ablation and 5.6% with large loop excision of transformation zone (LLETZ). Full visibility of the squamocolumnar junction, necessary for optimal visual triage and ablation, declined from 68.5% at age 30 to 35.4% at age 49. CIN2+ and CIN3+ (CIN- Cervical intraepithelial neoplasia), including five cancers, were identified by histology in 5.9 and 3.2% of the HPV-positive women, respectively (0.9 and 0.5% of the total screening population), leading to additional treatment as indicated. The prevalences of HPV infection and CIN2+ were substantially higher (40.5 and 2.5%, respectively) among WLWH. Colposcopic impression led to over- and under-treatment compared to the histopathology reference standard. CONCLUSION: A cervical cancer screening program using self-sampled HPV testing, with colposcopic immediate management of women positive for HPV, proved feasible in Nigeria. Based on the collected specimens and images, we are now evaluating the use of a combination of partial HPV typing and automated visual evaluation (AVE) of cervical images to improve the accuracy of the screening program.

What is the price of prevention? New evidence from a field experiment.

How does increasing access to treatment affect the demand for preventive testing? In this paper we present results from a field experiment in Nigeria in which we offered cervical cancer screening to women at randomly chosen prices. To test our hypothesis, we also offered women a lottery where the payoff was a subsidy towards the cost of cervical cancer treatment (conditional upon a diagnosis of cervical cancer). We find that women randomly selected to receive the conditional cancer treatment subsidy were about 4 percentage points more likely to take up screening than those in the control group. We also show that reducing the price of screening by 10 cents increased take-up by about 1 percentage point. These results offer compelling evidence that the optimal set of subsidies to increase take-up of preventive testing in developing countries, must include subsidies towards treatment costs (in addition to price subsidies).