HPV self-testing for primary cervical cancer screening in Madagascar: VIA/VILI triage compliance in HPV-positive women.

OBJECTIVE: To assess triage compliance and the effect of the time from screening to triage on follow-up among HPV-positive women. METHODS: We recruited 1232 women in a screening campaign in Madagascar from February to October 2015. In the first period (February-May), HPV tests were performed remotely using the cobas test. In the second period (May-October), testing was performed on-site using the Xpert HPV assay. HPV-positive women were invited for triage with visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). Systematic biopsy and endocervical brushing were performed on all HPV-positive women for quality control. Three groups were defined according to time from HPV testing to triage invitation for HPV-positive women-Group I: delayed (> 3 months), Group II: prompt (24-48 hours), and Group III: immediate (< 24 hours). RESULTS: A total 1232 self-sampled HPV tests were performed in the study period (496 in Group I, 512 in Group II, and 224 in Group III). Participants' mean age was 43.2 ± 9.3 years. Mean time from screening to VIA/VILI testing was 103.5 ± 43.6 days. Overall HPV prevalence was 28.0%. HPV prevalence was 27.2% in Group I (cobas test), 29.2% in Group 2 (Xpert test), and 26,7% in Group III (Xpert test). The VIA/VILI compliance rate was 77.8% for Group I, 82.7% for Group II, and 95.0% for Group III. Of women undergoing VIA/VILI, 56.3% in Group I and 43.5% in Groups II/III had positive results. Prevalence of cervical intraepithelial neoplasia grade 2 or worse among HPV-positive women was 9.8% for Group I and 6.8% for Groups II/III. Non-adherence was higher among rural women, uneducated women, and women in Group I. CONCLUSION: HPV-positive women with immediate VIA/VILI triage invitation had the best triage compliance. A single-day test and triage strategy is preferred for low-resource settings.

PERFORMANCE OF SMARTPHONE-BASED DIGITAL IMAGES FOR CERVICAL CANCER SCREENING IN A LOW-RESOURCE CONTEXT.

OBJECTIVES: Colposcopes are expensive, heavy, and need specialized technical service, which may outreach the capacity of low-resource settings. Our aim was to assess the performance of smartphone-based digital images for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Human papillomavirus (HPV)-positive women recruited through a cervical cancer screening campaign had VIA/VILI assessment (visual inspection after application of acetic acid/lugol's iodine). Cervical digital images were captured with a smartphone camera, randomly coded with no prior selection and distributed on an online database (Google Forms) for evaluation. Healthcare providers were invited to evaluate the images and identify CIN2+. The gold standard was the histopathological diagnosis. The sensitivity and specificity for the detection of CIN2+ was assessed for each reader and reported with the 95 percent confidence interval (Clopper-Pearson method). RESULTS: One hundred twenty-five consecutive HPV-positive women were included, with 19 CIN2+ (15.2 percent). Forty-five gynecologists completed the assessment, one-third were considered as experts (>50 colposcopies) and two-thirds as novices (<50 colposcopies). The sensitivity and specificity for CIN 2+ detection was 71.3 percent (67.0-75.7 percent) and 62.4 percent (57.5-67.4 percent), respectively. The performance of novices and experts was similar. The readers assessed 73.1 percent of images as acceptable for diagnostic. CONCLUSION: Smartphone-based digital images, with its high portability, have a great potential for the diagnosis of CIN2+ in low-resource context.

A Mobile Health Data Collection System for Remote Areas to Monitor Women Participating in a Cervical Cancer Screening Campaign.

BACKGROUND: Barriers to efficient cervical cancer screening in low- and medium-income countries include the lack of systematic monitoring of the participants' data. The aim of this study was to assess the feasibility of a mobile health (m-Health) data collection system to facilitate monitoring of women participating to cervical cancer screening campaign. METHODS: Women aged 30-65 years, participating in a cervical cancer screening campaign in Ambanja, Madagascar, were invited to participate in the study. Cervical Cancer Prevention System, an m-Health application, allows the registration of clinical data, while women are undergoing cervical cancer screening. All data registered in the smartphone were transmitted onto a secure, Web-based platform through the use of an Internet connection. Healthcare providers had access to the central database and could use it for the follow-up visits. Quality of data was assessed by computing the percentage of key data missing. RESULTS: A total of 151 women were recruited in the study. Mean age of participants was 41.8 years. The percentage of missing data for the key variables was less than 0.02%, corresponding to one woman's medical history data, which was not sent to the central database. Technical problems, including transmission of photos, human papillomavirus test results, and pelvic examination data, have subsequently been solved through a system update. CONCLUSION: The quality of the data was satisfactory and allowed monitoring of cervical cancer screening data of participants. Larger studies evaluating the efficacy of the system for the women's follow-up are needed in order to confirm its efficiency on a long-term scale.

A Smartphone-Based Approach for Triage of Human Papillomavirus-Positive Sub-Saharan African Women: A Prospective Study.

BACKGROUND: Sub-Saharan African countries are marked by a high incidence of cervical cancer. Madagascar ranks 11th among the countries with the highest cervical cancer incidence worldwide. OBJECTIVE: The aim of the study was to evaluate the performances of digital smartphone-based visual inspection with acetic acid (D-VIA) and Lugol's iodine (D-VILI) for diagnosing cervical precancer and cancer. METHODS: Human papillomavirus (HPV)-positive women recruited through a cervical screening campaign had D-VIA and D-VILI examinations with endocervical curettage (ECC) and cervical biopsy. Three images were captured for each woman (native, D-VIA, D-VILI) using a smartphone camera. The images were randomly coded and distributed on 2 online databases (Google Forms). The D-VIA form included native and D-VIA images, and the D-VILI form included native and D-VILI images. Pathological cases were defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Physicians rated the images as non-pathological or pathological. Using the ECC and cervical biopsy results as references, the sensitivity and specificity of D-VIA and D-VILI examinations for each and all physicians were calculated. RESULTS: Altogether, 15 clinicians assessed 240 images. Sensitivity was higher for the D-VIA interpretations (94.1%; 95% CI 81.6-98.3) than for the D-VILI interpretations (78.8%; 95% CI 54.1-92.1; P=.009). In contrast, the specificity was higher for the D-VILI interpretations (56.4%; 95% CI 38.3-72.9) than for the D-VIA interpretations (50.4%; 95% CI 35.9-64.8; P=.005). CONCLUSION: Smartphone-based image for triage of HPV-positive women is more accurate for detecting CIN2+ lesions with D-VIA than D-VILI, although with a small loss of specificity.

Usability and feasibility of a mobile health system to provide comprehensive antenatal care in low-income countries: PANDA mHealth pilot study in Madagascar.

Background Madagascar's maternal health mortality ratio in 2013 was 478 deaths per 100,000 live births. Most deaths are related to direct complications during pregnancy and childbirth and could be reduced by providing comprehensive antenatal care (ANC). Objective The objective of the study was to assess the usability and feasibility of a mobile health system (mHealth) to provide high-quality ANC, according to World Health Organization (WHO) recommendations. Methods PANDA (Pregnancy And Newborn Diagnostic Assessment) is an easy-to-use mHealth system that uses affordable communications technology to support diagnosis and health care worker decision-making regarding ANC. From January to March 2015, a cross-sectional pilot study was conducted in Ambanja District, Madagascar, in which ANC using PANDA was provided to 100 pregnant women. The collected data were transmitted to a database in the referral hospital to create individual electronic patient records. Accuracy and completeness of the data were closely controlled. The PANDA software was assessed and the number of abnormal results, treatments performed, and participants requiring referral to health care facilities were monitored. Results The PANDA system facilitated creation of individual electronic patient records that included socio-demographic and medical data for 100 participants. Duration of ANC visits averaged 29.6 min. Health care providers were able to collect all variables (100%) describing personal and medical data. No major technical problems were encountered and no data were lost. During 17 ANC visits (17%), an alert function was generated to highlight abnormal clinical results requiring therapy or referral to an affiliated hospital. Participants' acceptability of the system was very high. Conclusion This pilot study proved the usability and feasibility of the PANDA mHealth system to conduct complete and standardised ANC visits according to WHO guidelines, thus providing a promising solution to increase access to high-quality and standardised ANC for pregnant women in remote areas.

Human papillomavirus prevalence and type-specific distribution of high- and low-risk genotypes among Malagasy women living in urban and rural areas.

BACKGROUND: Cervical cancer (CC) is the most common cancer among sub-Saharan African women. Efficient, global reduction of CC will only be achieved by incorporation of human papillomavirus (HPV) vaccination into existing programmes. We aimed to investigate the overall and type-specific prevalences and distributions of oncogenic HPVs. METHODS: A total of 1081 women aged 30-65 years were recruited to three sequential studies in Madagascar. Demographic and historical data were obtained from participants, and specimens were self-collected for HPV testing using real-time polymerase chain reaction. HPV-positive women underwent detailed pelvic examination, visual inspection of the cervix with acetic acid, biopsy, and endocervical curettage. Data were analysed using χ(2) and t-tests, and logistic regression. RESULTS: The prevalence of all 19 high-risk types of HPV was 39.3%. There were no differences in the prevalences of HPV and CC between rural and urban Malagasy women. The most common high-risk HPV types were HPV-53 (6.2%) and HPV-68 (5.8%), followed by HPV-52 (5.2%), HPV-35 (4.5%), HPV-73 (3.4%), HPV-31 (3.4%), HPV-16 (3.1%), and HPV-18 (3.1%). The prevalence of cervical intraepithelial neoplasia≥grade 2 (CIN2+) was 9.4%. CIN1-CIN3 lesions were more common in women in their 30s. The median age of participants with CIN2+ was 44 years (range 37-55). Overall, 25.8% of CIN2+ cases were associated with HPV-16/18. CONCLUSIONS: This study provides evidence to support the introduction of HPV vaccination in eastern African countries such as Madagascar. Further studies are needed to screen younger women and adolescents, to provide a global vision of HPV genotype distributions and to maximize the impact of HPV vaccination.

Use of swabs for dry collection of self-samples to detect human papillomavirus among Malagasy women.

BACKGROUND: Most women in developing countries have never attended cervical screening programmes and often little information exists on type-specific human papillomavirus (HPV) prevalence among these populations. Self-sampling for HPV testing (self-HPV) using a dry swab may be useful for establishing a screening program and evaluating HPV prevalence. Our aim was to evaluate self-HPV using a dry swab stored at room temperature. METHODS: This community-based study in Madagascar consisted of 449 women aged 30-65. Eligible women were provided a dry swab to perform self-HPV. HPV analysis was accomplished by two different real-time PCR tests using the same extracted DNA from the samples. RESULTS: Overall, 52 (11.6 %) specimens were invalid for HPV detection. The delay between sampling and laboratory processing of DNA extraction considerably increased invalid results. Overall HPV prevalence of 14 hrHPV types detected by the two PCR tests was found to be 38.2 % (n = 152). Distribution of 19 hrHPV and 9 low-risk HPV (lrHPV) types revealed most frequently 53 and 68 among hrHPV and HPV 54, HPV 70 and HPV 42 among lrHPV. Agreement between the two PCR methods for any of the 14 high-risk HPV (hrHPV) strains detected was 89.9 % (kappa = 0.77, 95 % CI: 0.71-0.84). In 385 (85.7 %) samples the DNA load of ß-globin demonstrated a signal with medium or high level copies. Conversely, in 28 (60.9 %) invalid samples the signal was undetectable. The HPV-DNA load signal was predominantly of intermediate level (58.5 %, n = 218). CONCLUSIONS: Self-HPV using a dry swab stored at room temperature could be a useful method for HPV screening and for conducting population-based surveys on HPV prevalence in resource-poor settings.

Use of Smartphones as Adjuvant Tools for Cervical Cancer Screening in Low-Resource Settings.

OBJECTIVES: Our aim was to evaluate the feasibility and performance of smartphone digital images for the detection of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as an adjunct to a conventional visual inspection approach with acetic acid (VIA) and Lugol's iodine (VILI), in comparison with detection by histopathologic examination. METHODS: Three hundred women were primarily screened for human papillomavirus (HPV) using self-collected vaginal specimens. Human papillomavirus-positive women were then invited for VIA and VILI, which were interpreted as (i) nonpathological, (ii) pathological or, (iii) inconclusive. Cervical smearing, endocervical brushing, and cervical biopsies were performed. Digital images of the cervix were taken with a smartphone and evaluated offsite by experienced health care providers. Sensitivity and specificity for CIN2+ were compared between on-site and off-site observers, using histopathological diagnosis as the criterion standard. RESULTS: Eighty-eight HPV-positive women were screened for cervical cancer. Overall, 7 cases of CIN2+ (8.0%) were diagnosed using biopsy specimens. The on-site physician obtained a sensitivity of 28.6% (95% confidence interval [95% CI], 3.7-71) and a specificity of 87.2% (95% CI, 77.7- 93.7). The off-site physicians obtained a sensitivity ranging between 42.9% (95% CI, 9.9-81.6; p = 1) and 85.7% (95% CI, 42.1-99.6; p = .13) and a specificity between 48.1% (95% CI, 36.5- 59.7; p < .001) and 79.2% (95% CI, 68.5-87.6; p = .10). Comparison between observers did not reach significance. Observers assessed 95.6% of all images as very good or acceptable for interpretation purpose. CONCLUSION: Smartphone images may be a useful adjunct to conventional VIA and VILI for the detection of CIN2+ and improve cervical cancer screening in low-resource settings.