The journey of cancer patients and the quest to equity: findings from Morocco.

OBJECTIVES: Rapid diagnostic and assessment pathways for cancer patients provide timely and effective care. This study took place in Morocco, where the majority of patients treated in the public sector are diagnosed at an advanced stage. The aim of this study was to determine the duration of different time intervals along the cancer patient pathway and to highlight problem areas so that strategies can be implemented to make the process more equitable and effective. STUDY DESIGN: Cross-sectional study. METHODS: Recently diagnosed cancer patients were recruited from four major oncology centres in Morocco; namely, Marrakech, Casablanca, Rabat, and Fez. A questionnaire survey was administered, including sociodemographic and medical information and questions on access to the oncology centre, beliefs, and opinions on the medical staff. The dates of symptom recognition, assessment, diagnosis referral, biopsy, and treatment initiation were collected. Different time intervals (patient, diagnosis, biopsy, and treatment) were estimated and their determinants were investigated. RESULTS: A total of 812 patients were interviewed. The majority of participants were breast cancer patients. In total, 60% of participants were at stage III-IV. The main facilitators of cancer diagnosis confirmation and treatment initiation were easy access to diagnosis and treatment facilities, financial resources, personal history of cancer, time availability, late stage at diagnosis, advanced age, and private health insurance. The patient interval (i.e., time from symptom recognition to initial healthcare assessment) had a median duration of 30 days. The biopsy and treatment intervals were within the current international recommendations (7 and 28 days, respectively). However, the diagnosis interval (52 days) was twice as long as the recommended timeframes from the UK, Australia, and the World Health Organization (<28 days). CONCLUSIONS: Interval targets should be defined to encourage health systems to be more equitable and effective and to ensure that cancer patients are treated within a defined timeframe.

HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers.

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co-infection in this region. We studied 92 patients HBsAg(+) /anti-HDV IgG(+) followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV-3) was found in all of the HBV/HDV-infected patients that could be genotyped for HDV, confirming that HDV-3 can associate with non-F HBV genotypes. However, a HDV-3 mutant was found in 29.3% of patients and was more frequently associated with non-F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV-3 with non-F HBV genotypes.

Meta-analysis of the efficacy of cold coagulation as a treatment method for cervical intraepithelial neoplasia: a systematic review.

BACKGROUND: Cold coagulation is an ablative method for treatment of cervical intraepithelial neoplasia (CIN). Despite reports of efficacy against all grades of CIN (CIN1-3), cold coagulation has been infrequently used since the 1980s, and was absent from the recent Cochrane review on CIN treatment. OBJECTIVES: To provide a systematic review of cold coagulation efficacy and acceptability for CIN treatment through meta-analysis of clinical reports and a randomised control trial. SEARCH STRATEGY: A literature search in PubMed, Web of Science, EMBASE, and regional databases yielded 388 papers. Title, abstract and/or reference list review identified 22 papers describing cold coagulation treatment of CIN, with 13 providing adequate data for inclusion in the meta-analysis. SELECTION CRITERIA: Publications or conference abstracts describing original data (number of women treated, followed up and cured, provider type, cure definition) were retained. No language or publication date limitations were imposed. DATA COLLECTION AND ANALYSIS: Data extracted from 13 studies were pooled, and statistical analyses of proportion cured were conducted with data stratified by lesion grade and study region. MAIN RESULTS: Among 4569 CIN patients treated with cold coagulation, summary proportion cured of 96% [95% confidence interval (CI) 92-99%] and 95% (92-98%) were obtained for CIN1 and CIN2-3 disease, respectively. Side-effects and adverse effects were infrequent, and fertility was not impaired. CONCLUSIONS: Cold coagulation CIN cure rates were comparable to those of other excisional and ablative methods. Cold coagulation is indicated for all grades of CIN, is safe, quick and acceptable, and may be of particular relevance for use in resource-limited settings.

Can visual cervical screening be sustained in routine health services? Experience from Mali, Africa.

OBJECTIVE: To assess the feasibility of sustaining visual cervical screening and treatment services in Mali, and to evaluate their performance and impact in improving the provision of cervical cancer control, following an initial cross-sectional study. DESIGN: Descriptive study. SETTING: Bamako area, Mali. POPULATION: Women aged 30-59 years. METHODS: Routine visual screening and treatment services were organised through two hospitals and 14 health centres. Patients with positive visual screening tests underwent colposcopy and/or directed biopsies, and ablative or surgical excision treatment was offered to those with cervical intraepithelial neoplasia (CIN). MAIN OUTCOME MEASURES: Test positivity, detection and treatment rates for CIN and the sustainability of screening services. RESULTS: Of the 14,141 women screened, 1682 (11.9%) were positive and were referred for further investigations and treatment. Over 75% of the screen-positive women underwent colposcopy and/or biopsy. CIN 1 was detected in 383 women, CIN 2 in 88, CIN 3 in 37 and invasive cervical cancer in 497. More than 80% of women with CIN and 35% of those with invasive cancer received treatment. The test performance characteristics and treatment coverage of routine screening were similar to those observed in the preceding cross-sectional study. CONCLUSION: Visual screening and treatment services are sustainable and effective in improving cervical cancer control provision by health services in Bamako, Mali. It is essential to organise and sustain several point-of-care services in order to extend cervical cancer prevention in low-income African countries.

Risk of seropositivity to multiple oncogenic human papillomavirus types among human immunodeficiency virus-positive and -negative Ugandan women.

To understand the prospects for human papillomavirus (HPV) mass vaccination in the setting of a developing country, we studied the co-occurrence of seropositivity to multiple high-risk (hr) HPV types among HIV-positive and HIV-negative Ugandan women. Our seroepidemiological study was conducted among 2053 women attending antenatal clinics. Sera were analysed for antibodies to eight hrHPV types of the α-7 (18/45) and α-9 (16/31/33/35/52/58) species of HPV by using a multiplex serology assay. Our results show that seropositivity for greater than one hrHPV type was as common (18 %) as for a single type (18 %). HIV-positive women had higher HPV16, HPV18 and HPV45 seroprevalences than HIV-negative women. In multivariate logistic regression analysis, age (>30 years) and level of education (secondary school and above) reduced the risk, whereas parity (>5) and HIV-positivity increased the risk for multiple hrHPV seropositivity. However, in stepwise logistic regression analyses, HIV-status remained the only independent, stand-alone risk factor [odds ratio (OR) 1.7, 95 % confidence interval (CI) 1.0-2.8). On the other hand, the risk of HPV16 or HPV18 seropositive women, as compared to HPV16 or HPV18 seronegative women, for being seropositive to other hrHPV types was not significantly different when they were grouped by HIV-status (ORHPV16/HIV+ 12, 95 % CI 4.5-32 versus ORHPV16/HIV- 22, 95 % CI 15-31 and ORHPV18/HIV+ 58, 95 % CI 14-242 versus ORHPV18/HIV- 45, 95 % CI 31-65). In conclusion, seropositivity to HPV16, HPV18 and to non-vaccine hrHPV types is common in Ugandan women, suggesting that there is little natural cross-protective immunity between the types. HIV-positivity was an independent, stand-alone, albeit moderate risk factor for multiple hrHPV seropositivity. HPV mass vaccination may be the most appropriate method in the fight against cervical cancer in the Ugandan population.

Clinical trials of cancer screening in the developing world and their impact on cancer healthcare.

Several research and training initiatives were organized by the International Agency for Research on Cancer (IARC) in collaboration with national institutions in countries such as Angola, Brazil, Burkina Faso, China, Republic of Congo, Guinea, India, Mali, Mauritania, Nepal, Niger, Peru, Tanzania and Thailand among others, to address feasible and effective means of early detection and prevention of cervical, breast and oral cancers. The impact of these activities, that involved over 600 000 participants and more than 1200 healthcare personnel trained on strengthening the local health services in terms of infrastructure, human resources and service delivery aspects in host countries and other regions, is addressed here. These studies, inbuilt in appropriate health services platforms, have resulted in the development and sustenance of several continuing point of care services of screening and treatment in most host countries, particularly in sub-Saharan Africa, and have catalysed regional early detection programmes in India, China and Thailand. The IARC collaborative studies have evolved into major focal points of training and extending services in many countries. The large evidence base, resulting from ours and other studies is likely, in due course, to facilitate much wider scaling up of screening and treatment services through organised programmes.

Performance of colposcopy in five sub-Saharan African countries.

OBJECTIVE: The performance of colposcopy provided in a screening study in five African countries was evaluated. DESIGN: Cross-sectional study. SETTING: Burkina Faso, Congo Brazzaville, Guinea Conakry, Mali and Niger. POPULATION: Women aged 25-59 years. METHODS: A total of 29 294 women participated in a cervical screening study in the five study sites, and newly trained local doctors performed colposcopy and directed biopsies as indicated. Using meta-analytical tools, four measures of colposcopy performance at different thresholds of colposcopic abnormalities were assessed. Sources of heterogeneity were also assessed. MAIN OUTCOME MEASURES: Proportions of women receiving biopsies, adequate biopsies and women diagnosed with cervical intraepithelial neoplasia (CIN). RESULTS: Among 28 553 women with satisfactory colposcopy, 3101 had a colposcopic diagnosis of probable low-grade or worse lesions and 1128 probable high-grade or worse lesions. Overall, the measures that reached the set standards were proportion of biopsy taken at colposcopy threshold of probable high-grade or worse lesions (95%, 95% CI 90-100%) and proportion of adequate biopsy samples. The set standards were not met for the proportions of women diagnosed with CIN at different colposcopic abnormality thresholds. Detection of CIN2 or worse lesions increased with increasing colposcopic abnormality. CONCLUSIONS: The performance of colposcopy in some of the African sites studied was comparable to that previously observed in other studies. With appropriate training, monitoring, continuing practice and quality assurance, adequate standards of colposcopy can be attained in sub-Saharan Africa.

Accuracy of conventional cytology: results from a multicentre screening study in India.

OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in five cross-sectional studies. Three thresholds were used to define test positivity: atypical squamous cells of uncertain significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for final disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically confirmed HSIL. RESULTS: The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A significantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. CONCLUSION: The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and specificity.

Human papillomavirus infection among human immunodeficiency virus-infected women in Maharashtra, India.

INTRODUCTION: Frequency and distribution of HPV types in HIV-infected women with and without cervical neoplasia and their determinants have not been widely studied in India. We report and discuss HPV prevalence and type distribution in HIV-infected women. METHODS: HPV genotyping was done using cervical samples from 1109 HIV-infected women in a cross-sectional study. RESULTS: Any HPV was detected in 44.8% and high-risk ones in 41.0% women. Frequency of single and multiple high-risk infections were 26.7% and 14.3%, respectively. Frequencies of high-risk HPV infections in women with and without cervical neoplasia were 73.5% and 37.6%, respectively. HPV16 was the most common genotype, present in 11.5%, and 58.5% of women with cervical intraepithelial neoplasia (CIN) 2 and 3. Other most common high-risk HPV types in CIN 2-3 lesions were HPV 31 (22.6%); 56 (13.2%); 18 and 68a (11.3%) and 33, 35 and 51 (9.4%); and 70 (7.5%). Women under 30 or over 44 years, no abortions, and women with diagnosis of HIV infection within the last 5 years were at high risk of multiple oncogenic HPV infection. CONCLUSION: We observed a very high frequency of high-risk HPV and multiple infections in HIV-infected women.

Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis.

The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose-response meta-analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m(-2) increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist-to-hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer.