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.

Prevalence and risk factors for urinary incontinence in pregnancy in Ikere-Ekiti, Nigeria.

AIMS: The objective of this study was to determine the prevalence and associated risk factors for urinary incontinence (UI) among antenatal clinic attendees in a low resourced setting in Nigeria. METHODS: This study was a cross-sectional study involving pregnant women aged 18-45 years. Data was obtained from 442 pregnant women using the English version International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short form (ICIQ-UI-SF) from July 2017-September 2017. The questionnaires were self-administered. Data was analyzed with SPSS version 20. Logistic regression was also used to derive the adjusted odds ratio for risk factors of urinary incontinence among the respondents. A P-value <0.05 was taken as statistically significant. RESULTS: The prevalence of urinary incontinence in this study was 28.1%. UI prevalence among the nulliparous and multiparous women were 28.7% and 27.7% respectively. Stress urinary incontinence was the commonest (17.4%) while sexual relation was the most affected lifestyle (22.6%). Overweight (AOR 1.39, P = 0.03), obesity (AOR 1.60, P = 0.009), third trimester (AOR 2.09, P = 0.011), previous instrumental vaginal delivery (AOR 11.54, P < 0.001), Ibo tribe (AOR 3.29, P = 0.006); and Ebira tribe (AOR 8.86, P = 0.028) were associated with UI in pregnancy. CONCLUSION: Urinary incontinence affects more than a quarter of pregnant women; with substantial lifestyle changes; and sexual relation is the most affected activity. Health care providers should endeavor to enquire about symptoms of UI among pregnant women. Efficacy of interventions needs to be investigated in this population.

PENTAZOCINE VERSUS PENTAZOCINE WITH RECTAL DICLOFENAC FOR POSTOPERATIVE PAIN RELIEF AFTER CESAREAN SECTION- A DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED TRIAL IN A LOW RESOURCE AREA.

BACKGROUND: The unimodal approach of using pentazocine as post-cesarean section pain relief is inadequate, hence the need for a safer, easily available and more effective multimodal approach. AIM: To evaluate the effectiveness of rectal diclofenac combined with intramuscular pentazocine for postoperative pain following cesarean section. METHODS: In this double blind clinical trial, 130 pregnant women scheduled for cesarean section under spinal anesthesia were randomly assigned to two groups. Group A received 100mg diclofenac suppository and group B received placebo suppository immediately following surgery, 12 and 24h later. Both groups also received intramuscular pentazocine 30mg immediately following surgery and 6 hourly postoperatively in the first 24 h. Postoperative pain was assessed by visual analogue scale at end of surgery and 2, 12 and 24 h after surgery. Patient satisfaction scores were also assessed. RESULTS: One hundred and sixteen patients completed the study. Combining diclofenac and pentazocine had statistically significant reduction in pain intensity at 2, 12, and 24 hours postoperatively compared to pentazocine alone (p <0.05). No significant side effects were noted in both groups. The combined group also had significantly better patient satisfaction scores. CONCLUSION: The addition of diclofenac suppository to intramuscular pentazocine provides better pain relief after cesarean section and increased patient satisfaction.

The age-specific prevalence of human papillomavirus and risk of cytologic abnormalities in rural Nigeria: implications for screen-and-treat strategies.

Cervical screening for carcinogenic human papillomavirus (HPV) infection is being considered for low-income countries. Effectiveness requires targeted screening in older women in whom prevalent infections are more likely to be persistent and predictive of precancer. Some studies in West Africa have found unusually high HPV prevalences across all adult ages, which may reduce the positive predictive value (PPV) of HPV-based screening, if positivity in older women does not sufficiently predict elevated risk. We conducted a population-based study in rural Nigeria to identify HPV prevalence and associated cervical abnormalities. Using stratified random sampling, we enrolled women age 15+. Nonvirgins had a cervical exam including liquid-based cytology and PCR HPV DNA testing from residual cytology specimens. Two-thirds of invited women participated, and 14.7% had detectable carcinogenic HPV, a proportion that did not decline with age (p-trend = 0.36) and showed slight peaks in the 15-29 and 60-69 age groups. Among women of the age typically considered for screen-and-treat programs (30-49 years), 12.8% were HPV positive, and the PPV for high-grade or worse cytology was 16.4%. Comparatively, women age < 30 were more likely to be HPV positive (18.9%, p = 0.03) with a lower PPV (4.2% p = 0.05). Among women age 50+ (typically excluded from screening in resource-poor settings because inexpensive treatment is not available), HPV positivity was 14.2% with a PPV of 13.9%. In Irun and similar settings where HPV does not decline with age, HPV-based screen-and-treat programs might be feasible for mid-adult women because prevalence is sufficiently low and positivity predicts elevated risk of more easily treated precancer.

Effectiveness of a simple rapid human papillomavirus DNA test in rural Nigeria.

Success of the new human papillomavirus (HPV) DNA test for low-resource settings (careHPV™ test; QIAGEN Gaithersburg Inc., Gaithersburg, MD) requires good test performance when operated by personnel with limited laboratory experience. We evaluated the transferability, reliability, and accuracy of the careHPV test nested within a cervical screening project in a large Nigerian village. CareHPV testing was performed on screen-positive (n = 345) and screen-negative (n = 42) women attending colposcopy (68.3% of referred). Biopsies of abnormal-appearing areas were processed and read in the U.S. CareHPV specimens taken immediately before colposcopy were processed up to four times (in the field) by two secondary school graduates without laboratory experience, trained for this study. Specifically, QIAGEN Gaithersburg trained a laboratory-inexperienced U.S. researcher, who trained the first local technician who, in turn, trained the second. Residual specimens were sent to the U.S. for MY09/MY11 PCR testing for 13 carcinogenic genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) plus HPV66 (included in careHPV). Intrarater agreement was 98.8% (κ = 0.97) and 98.9% (κ = 0.97) for Technicians 1 and 2, respectively, while inter-rater agreement was 96.3% (κ = 0.90). Agreement with MY09/MY11 PCR (virologic reference standard) was 89.3% (κ = 0.73) with 74.2% sensitivity and 95.7% specificity. The careHPV test detected 12 (80%) of 15 histologically confirmed cervical intraepithelial neoplasia Grade 2 (CIN2) or worse lesions, with an estimated 83.0% specificity to detect

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.

Clinical correlates of leiomyoma estrogen and progesterone receptors among Nigerian women.

OBJECTIVE: To compare the expression of estrogen receptor α (ERα) and progesterone receptor (PR) in myometrium and leiomyomata tissue, and to correlate their expression with symptoms of uterine leiomyomata. METHODS: In a cross-sectional study, intraoperative biopsy samples of leiomyomata and adjacent myometrial specimens were obtained from premenopausal women with uterine leiomyomata treated at a center in Nigeria between September 2013 and August 2014. Immunohistochemistry for ERα and PR expression was performed on the samples. The immunoscores of both receptors were correlated with the size and symptoms of the leiomyomata. RESULTS: Among 60 pairs of samples, leiomyomata had a higher mean expression of ERα (H-score 193.42±64.55 vs 153.29±69.13; P=0.01) and PR (214.86±66.56 vs 171.53±63.53; P<0.001) than did myometrial tissues. The tumor diameter correlated negatively with the immunoscores of both receptors irrespective of age, parity, and body mass index, but this was only significant for PR (ρ=-0.44; P<0.001). Downregulation of PR on leiomyomata was predicted to occur at a diameter of 11cm. Menorrhagia, dysmenorrhea, and infertility occurred independently of steroid-receptor expression. CONCLUSION: Leiomyomata seem to depend on steroid hormones, but only during early tumor development. This could have implications for the selection of patients for medical management, especially with steroid-receptor modulators.

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).

Total laparoscopic hysterectomy: A case report from ILE-IFE, Nigeria.

Total laparoscopic hysterectomy (TLH) is an advanced gynecological laparoscopic procedure that is widely performed in the developed world. However, its feasibility in resource-poor settings is hampered by obvious lack of equipments and/or skilled personnel. Indeed, TLH has never been reported from any Nigerian hospital. We present a 50-year-old multipara scheduled for hysterectomy on account of pre-malignant disease of the cervix, who had TLH with bilateral salpingo-oophorectomy in the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, southwestern Nigeria and was discharged home on the first post-operative day. She was seen in the gynecology clinic a week later in stable condition and she was highly pleased with the outcome of her surgery. This case is presented to highlight the attainability of operative gynecological laparoscopy, including advanced procedures like TLH in a resource-constrained setting, through the employment of adequate local adaptation and clever improvisation.

A population-based cross-sectional study of age-specific risk factors for high risk human papillomavirus prevalence in rural Nigeria.

BACKGROUND: Cervical cancer, caused by persistent infection with carcinogenic human papillomavirus (HR-HPV), is particularly prevalent in Sub-Saharan Africa and is associated with a high mortality rate. Some studies in West Africa, including our own, have found unusually high HR-HPV across all ages with a slight peak in older women. This increased prevalence at older ages may complicate screen-and-treat programs, which are implemented in regions where HPV prevalence declines with age and typically target women between 30-49 years. A better understanding of the determinants of high HR-HPV prevalence at older ages is needed. The goal of this study is to explore risk factors for HR-HPV prevalence by age among women in our population-based study in Irun, a rural town in southwestern Nigeria. METHODS: 1,420 women were administered a clinic-based questionnaire regarding sexual and reproductive behavior, marital status (including co-wives), and malaria exposure. Logistic regression compared questionnaire responses and PCR positivity for a set of 13 carcinogenic HR-HPV types. Results were stratified by age (15-29, 30-45, 46-55, and 56+ years). RESULTS: Birth control use and age at first pregnancy were associated with HR-HPV (p-value = 0.03 and 0.05, respectively). Early age at sexual debut and multiple sex partners were risks for HR-HPV, but did not reach significance (p-value = 0.1 and 0.07, respectively). Neither self-reported malaria nor presence of co-wives in the household was associated with HR-HPV (p-value = 0.85 and 0.24, respectively). In age sub-categories, early age at sexual debut was a significant risk factor for HR-HPV among women 35-45 years (p-value = 0.02). Early age at first pregnancy remained a significant risk factor for women aged 56+ years (p-value = 0.04). Greater than 2 sex partners and use of birth control were associated (though not significantly) with HR-HPV in women aged 30-45 (p-value = 0.08, respectively). CONCLUSIONS: In this high-risk region with elevated HR-HPV prevalence at older ages, we confirmed previously described, behavioral determinants of HR-HPV. There was no association with self-reported malaria or co-wives, which we had hypothesized might correlate with HR-HPV at older ages.