Feasibility of thermocoagulation in a screen-and-treat approach for the treatment of cervical precancerous lesions in sub-Saharan Africa.

BACKGROUND: The use of thermocoagulation for the treatment of cervical precancerous lesions has recently generated a great deal of interest. Our aim was to determine the feasibility of this outpatient procedure in the context of a cervical cancer (CC) screen-and-treat campaign in sub-Saharan Africa. METHODS: Between July and December 2015, women living in the area of Dschang (Cameroon) aged between 30 and 49 years, were enrolled in a CC screening study. HPV self-sampling was performed as a primary screening test and women who were either "HPV 16/18/45-positive" or "positive to other HPV types and to VIA" were considered screen-positive, thus requiring further management. The primary outcome was the percentage of screen-positive patients who met the criteria to undergo thermocoagulation. The secondary outcome was the assessment of the procedure's side effects immediately after treatment and at the 1-month follow-up visit. RESULTS: A total of 1012 women were recruited in the study period. Among 121 screen-positive women, 110 of them (90.9%) were eligible to be treated with thermocoagulation. No patients discontinued treatment because of pain or other side effects. The mean ± SD (Standard Deviation) score measured on the 10-point Visual Analogue Scale (VAS) was 3.0 ± 1.6. Women having less than 2 children were more likely to report a higher pain score than those with more than two (4.2 ± 2.0 versus 2.9 ± 1.5, respectively; p value = 0.016). A total of 109/110 (99.1%) patients came to the 1-month follow-up visit. Vaginal discharge was reported in 108/109 (99.1%) patients throughout the month following treatment. Three patients (2.8%) developed vaginal infection requiring local antibiotics. No hospitalizations were required. CONCLUSION: The majority of screen-positive women met the criteria and could be treated by thermocoagulation. The procedure was associated to minor side effects and is overall feasible in the context of a CC screen-and-treat campaign in sub-Saharan Africa. TRIAL REGISTRATION: The trial was retrospectively registered on November 11, 2015 with the identifier: ISRCTN99459678 .

Barriers to Cervical Cancer Screening in Geneva (DEPIST Study).

OBJECTIVES: Cervical screening is only efficient if a large part of eligible women participate. Our aim was to identify sociodemographic barriers to cervical screening and consider self-reported reasons to postpone screening. METHODS: Between September 2011 and June 2015, a questionnaire addressing reasons for nonparticipation in cervical screening was completed by 556 women who had not undergone a Pap test in the preceding 3 years. Pearson χ test was used to analyze differences between subgroups. Logistic regression was used to explore the association between sociodemographic characteristics and reasons for nonparticipation. RESULTS: The main reasons for nonparticipation in cervical cancer screening were practical barriers, such as lack of time and the cost of screening. These barriers were more likely to be reported by working women, women who were not sexually active, and those without health insurance. Younger women, non-European women living in Switzerland, and childless women were more likely to have never participated in a screening program before (adjusted odds ratio [aOR], 3.15; 95% CI, 1.41-6.98; aOR, 2.76; 95% CI, 1.48-5.16; aOR, 1.74; 95% CI, 1.03-2.99, respectively). CONCLUSIONS: Practical considerations seem to play a more important role in screening participation than emotional reasons and other beliefs. Particular attention should be paid to immigrant communities, where women seem more likely to skip cervical screening.

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.

HPV self-sampling in the follow-up of women after treatment of cervical intra-epithelial neoplasia: A prospective study in a high-income country.

Current follow-up strategy for women after large loop excision of the transformation zone (LLETZ) for cervical intra-epithelial neoplasia (CIN) is burdened by a low compliance. We evaluated the performance of home-based Human Papillomavirus (HPV) self-sampling (Self-HPV) after treatment for CIN with the aim to assess the (i) feasibility and (ii) follow-up compliance. This study took place at the Geneva University Hospitals between May 2016 and September 2020. Women aged 18 years or older, undergoing LLETZ for a biopsy-proven cervical intraepithelial neoplasia grade 1 or worse (CIN1 + ) were invited to participate. Agreement statistics, interpreted according to the scale of κ values, were calculated for Self-HPV and HPV performed by the physician (Dr-HPV). The samples were analyzed using GeneXpert and Cobas. Sample size was calculated to provide a 10% precision to estimate the kappa coefficient. A total of 127 women were included, with a median age of 35 years (interquartile range 30-41 years). There was a substantial agreement between Self-HPV and Dr-HPV using GeneXpert at 6 and 12 months, with a κ value of 0.63 (95%CI: 0.47-0.79) and 0.66 (95%CI: 0.50-0.82), respectively. Up to 9/10 (90%) women who did not come to their follow-up visit did not send their Self-HPV, either. In the follow-up after LLETZ treatment, home-based self-HPV is feasible, with substantial agreement between the two groups, however, concern remains regarding adherence to Self-HPV performance at home and loss to follow-up. The trial was registered on clinicaltrials.gov with the identifier NCT02780960.

Gestational trophoblastic disease in Switzerland: retrospective study of the impact of a regional reference centre.

AIMS OF THE STUDY: The European Society of Medical Oncology (ESMO) recommends that countries should have reference centres to provide adequate diagnosis and treatment of gestational trophoblastic disease. A trophoblastic disease centre in the French-speaking part of Switzerland was inaugurated in 2009. The objectives of this study were to report the activity of the centre during the last 10 years and analyse gestational trophoblastic disease outcomes. METHODS: This was a retrospective study with data collected from all cases of gestational trophoblastic disease referred to the centre from 2009 to 2018. All histological specimens as well as data for treatment and follow-up of gestational trophoblastic disease and neoplasia were reviewed. Clinical features, including age, prognostic score and International Federation of Gynecology and Obstetrics (FIGO) stages (in the case of gestational trophoblastic neoplasia), human chorionic gonadotropin (hCG) follow-up, treatment and outcome were reported. RESULTS: The centre registered 354 patients, and these patients presented 156 cases of partial hydatidiform moles, 163 cases of complete hydatidiform moles and 14 cases of gestational trophoblastic neoplasia. During follow-up, 35 gestational trophoblastic neoplasms were diagnosed after hCG persistence. After pathology review, the overall agreement rates between our centre and a participating provider hospital was 82%. Methotrexate was the first line of single-agent chemotherapy for most patients, with resistance rates of 23%. Multi-agent chemotherapy was used as first-line treatment for five patients. None of the patients followed up by the centre died from gestational trophoblastic disease. CONCLUSIONS: This study reflects the activity of the Swiss trophoblastic disease centre from the French-speaking part of Switzerland created in 2009, and its role as local and national reference centre, in terms of global health, for women with gestational trophoblastic disease.

Accuracy of self-collected vaginal dry swabs using the Xpert human papillomavirus assay.

BACKGROUND: Polymerase chain reaction-based Xpert human papillomavirus (HPV) assay is a rapid test that detects high-risk HPV (hrHPV) infection. This point-of-care test is usually performed by collecting a cervical specimen in a vial of PreservCyt® transport medium. We compared HPV test positivity and accuracy between self-collected sample with a dry swab (s-DRY) versus physician-collected cervical sampling using a broom like brush and immediate immersion in PreservCyt (dr-WET). METHODS: In this cross-sectional study, we recruited 150 women ≥ 18 years old attending the colposcopy clinic in the University Hospital of Geneva. Each participant first self-collected a vaginal sample using a dry swab and then the physician collected a cervical specimen in PreservCyt. HPV analysis was performed with Xpert. Part of the PreservCyt-collected sample was used for hrHPV detection with the cobas® HPV test. HPV test positivity and performance of the two collection methods was compared. RESULTS: HPV positivity was 49.1% for s-DRY, 41.8% for dr-WET and 46.2% for cobas. Good agreement was found between s-DRY and dr-WET samples (kappa±Standard error (SE) = 0.64±0.09,), particularly for low-grade squamous intraepithelial lesions (LSIL+) (kappa±SE = 0.80±0.17). Excellent agreement was found between the two samples for HPV16 detection in general (kappa±SE = 0.91±0.09) and among LSIL+ lesions (kappa±SE = 1.00±0.17). Sensitivities and specificities were, respectively, 84.2% and 47.1%(s-DRY), 73.1% and 58.7%. (dr-WET) and 77.8% and 45.7% (cobas) for CIN2+ detection. The median delay between sampling and HPV analysis was 7 days for the Xpert HPV assay and 19 days for cobas. There were 36 (24.0%) invalid results among s-DRY samples and 4 (2.7%) among dr-WET (p = 0.001). Invalid results happened due to the long interval between collection and analysis. CONCLUSION: Self-collected vaginal dry swabs are a valid alternative to collecting cervical samples in PreservCyt solution for HPV testing with the Xpert HPV assay. IMPACT: HPV self-collection with dry cotton swabs might assist in the implementation of an effective screening strategy in developing countries. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Registry ISRCTN83050913.

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.

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.

Web-based instrument to assess skills in visual inspection of the cervix among healthcare providers.

OBJECTIVE: To validate a web-based instrument for assessing healthcare providers' skills in visual inspection with acetic acid or Lugol iodine (VIA/VILI) for the diagnosis and management of cervical intraepithelial neoplasia. METHODS: An observational cross-sectional study enrolled healthcare providers in a web-based assessment of VIA/VILI skills between August and November 2014. Participants participated in a four-module training course, followed by a multiple-choice test with 70 questions based on cervical photographs of HPV-positive women participating in cervical screening. Logistic regression was used to identify relationships between independent variables and success on the test. RESULTS: Overall, 255 participants completed the test and 99 (38.8%) passed. No correlation was found between age or sex and test performance. Compared with other healthcare workers, physicians (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.01-3.63; P=0.048), and participants with more colposcopy experience (OR 3.62, 95% CI 1.91-6.85; P<0.001) and postgraduate VIA/VILI training (OR 1.95, 95% CI 1.16-3.29; P=0.012) were more likely to pass the test. Participants who repeated the test (31/255 [12.2%]) were five times more likely to succeed on their second repeat (OR 5.89, 95% CI 1.46-23.73; P=0.013). CONCLUSION: Web-based training for VIA/VILI is feasible and can identify healthcare workers who are proficient in this technique.

Randomized Comparison of Two Vaginal Self-Sampling Methods for Human Papillomavirus Detection: Dry Swab versus FTA Cartridge.

BACKGROUND: Human papillomavirus (HPV) self-sampling (self-HPV) is valuable in cervical cancer screening. HPV testing is usually performed on physician-collected cervical smears stored in liquid-based medium. Dry filters and swabs are an alternative. We evaluated the adequacy of self-HPV using two dry storage and transport devices, the FTA cartridge and swab. METHODS: A total of 130 women performed two consecutive self-HPV samples. Randomization determined which of the two tests was performed first: self-HPV using dry swabs (s-DRY) or vaginal specimen collection using a cytobrush applied to an FTA cartridge (s-FTA). After self-HPV, a physician collected a cervical sample using liquid-based medium (Dr-WET). HPV types were identified by real-time PCR. Agreement between collection methods was measured using the kappa statistic. RESULTS: HPV prevalence for high-risk types was 62.3% (95%CI: 53.7-70.2) detected by s-DRY, 56.2% (95%CI: 47.6-64.4) by Dr-WET, and 54.6% (95%CI: 46.1-62.9) by s-FTA. There was overall agreement of 70.8% between s-FTA and s-DRY samples (kappa = 0.34), and of 82.3% between self-HPV and Dr-WET samples (kappa = 0.56). Detection sensitivities for low-grade squamous intraepithelial lesion or worse (LSIL+) were: 64.0% (95%CI: 44.5-79.8) for s-FTA, 84.6% (95%CI: 66.5-93.9) for s-DRY, and 76.9% (95%CI: 58.0-89.0) for Dr-WET. The preferred self-collection method among patients was s-DRY (40.8% vs. 15.4%). Regarding costs, FTA card was five times more expensive than the swab (~5 US dollars (USD)/per card vs. ~1 USD/per swab). CONCLUSION: Self-HPV using dry swabs is sensitive for detecting LSIL+ and less expensive than s-FTA. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 43310942.

Smartphone Use for Cervical Cancer Screening in Low-Resource Countries: A Pilot Study Conducted in Madagascar.

BACKGROUND: Visual inspection of the cervix after application of 5% acetic acid (VIA) is a screening technique for cervical cancer used widely in low and middle-income countries (LMIC). To improve VIA screening performance, digital images after acid acetic application (D-VIA) are taken. The aim of this study was to evaluate the use of a smartphone for on- and off-site D-VIA diagnosis. MATERIALS AND METHODS: Women aged 30-65 years, living in the city of Ambanja, Madagascar, were recruited through a cervical cancer screening campaign. Each performed a human papillomavirus (HPV) self-sample as a primary screen. Women testing positive for HPV were referred for VIA followed by D-VIA, cervical biopsy and endocervical curettage according to routine protocol. In addition, the same day, the D-VIA was emailed to a tertiary care center for immediate assessment. Results were scored as either D-VIA normal or D-VIA abnormal, requiring immediate therapy or referral to a tertiary center. Each of the three off-site physicians were blinded to the result reported by the one on-site physician and each gave their individual assessment followed by a consensus diagnosis. Statistical analyses were conducted using STATA software. RESULTS: Of the 332 women recruited, 137 (41.2%) were HPV-positive and recalled for VIA triage; compliance with this invitation was 69.3% (n = 95). Cervical intraepithelial neoplasia was detected in 17.7% and 21.7% of digital images by on-site and off-site physicians, respectively. The on-site physician had a sensitivity of 66.7% (95%CI: 30.0-90.3) and a specificity of 85.7% (95%CI: 76.7-91.6); the off-site physician consensus sensitivity was 66.7% (95%CI: 30.0-90.3) with a specificity of 82.3% (95%CI: 72.4-89.1). CONCLUSION: This pilot study supports the use of telemedicine for off-site diagnosis of cervical intraepithelial neoplasia, with diagnostic performance similar to those achieved on-site. Further studies need to determine if smartphones can improve cervical cancer screening efficiency in LMIC.