The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Comparison of human papillomavirus-based cervical cancer screening strategies in Tanzania among women with and without HIV.

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)-based screening as a key element to eliminate the disease. In this cross-sectional study from Tanzania, we compared nine HPV-based cervical cancer screening strategies, including HPV testing at standard cut-off; HPV testing at increased viral load cut-offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO-LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high-grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut-off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV-: 91.5%), but moderate specificity (HIV+: 68.1%; HIV-: 85.7%). Increasing the cut-off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%-76.5%; HIV-: 89.5%-91.2%), with modest sensitivity reductions (HIV+: 91.3%-95.7%; HIV-: 83.5%-87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV-: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut-offs, may improve cervical cancer screening in Sub-Saharan Africa.

Distance to Health Care Facilities, Lifestyle Risk Factors, and Stage at Diagnosis in relation to Geographic Pattern of Esophageal Cancer in Tanzania, 2006-2016.

Esophageal cancer is an aggressive, often deadly disease globally that represents a significant health problem in Tanzania. The WHO reported 604,100 new esophageal cancer cases worldwide during 2020 and 544,076 deaths (Sung, 2021; World Health Organization, 2020). In Eastern Africa, 16,137 cases and 15,188 deaths were related to this disease in 2020. Esophageal cancer is associated with various etiologic risk factors, and access to the disease treatment is a major barrier to survival. This study examined associations between the prevalence of four geographically stratified, population-level, etiologic risk factors (tobacco use, unprotected water use, solid fuel source use, and poverty), as well as two access-to-care predictors (persons per hospital and distance from residence to where esophageal cancer treatment occurs). Regional- and coarser-scale zonal incidence rates were calculated for 2006 through 2016 and evaluated for geographic differences in relation to risk factors and access to care predictors using Poisson regression. Differences in the geographic distribution of esophageal cancer were observed. Distance from the region of residence to the treatment center (Ocean Road Cancer Institute) was statistically associated with the geographic pattern of esophageal cancer incidence. Further research into etiologic risk factors, dietary practices, and nutrition is needed to better understand the associations with esophageal cancer in Tanzania and other parts of Eastern Africa.

Return on Investment of a Breast Cancer Screening Program in Tanzania: Opportunity for Patient and Public Education.

Breast cancer is the second incident and second cause of cancer mortality among women in Tanzania due to late-stage presentation. The screening clinic at the Ocean Road Cancer Institute (ORCI) can help detect cases early and reduce cost of treatment. We calculated the return on investment (ROI) of the ORCI breast screening clinic. Screening and treatment data of all newly diagnosed breast cancer patients seen at ORCI during 2016-2018 were abstracted from the medical records. Also, data on time, resources, and cost of screening and treatment were obtained. The cost of treating screened patients was compared with cost of treating unscreened patients, and differences in cost of treatment were compared with cost of operating the screening program. Of the 730 total patients, 58 were screened prior to treatment, and 672 were not. There was no significant difference between stage at diagnosis and treatments received by screened and unscreened patients (79.3% late- stage vs 72.2% late-stage diagnosis, respectively (p = .531), or cost of treatment between the two groups (cost, in Tanzanian Shillings, for screened (2,167,155.14 or $954.27) vs unscreened (1,918,592.28 or $844.52), (p = .355). There was also no significant difference in cost of treatment between the screened and unscreened groups and a slightly negative ROI (- 0.05%) from implementing the program. The breast screening clinic in Tanzania has not yet proven its cost-effectiveness in reducing stage with screening. The likelihood that patients have utilized the clinic for treatment rather than early detection is a possible reason for the lack of cost-effectiveness. Future studies should focus on educational initiatives to encourage screening at early disease stage. Public education should increase awareness about the clinic for early detection. The experience of this program is ideal for dissemination to other low-income countries that are initiating cancer early detection and cancer education programs.

Field Research Experience of Medical Students: Learning and Translation from Global to Underserved US Settings.

While most medical schools in the USA provide opportunities for global health experiences, global health education is not included consistently or emphasized adequately in many medical school curricula. The City University of New York Medical School (CSOM) has a mission to educate and train students who are traditionally underrepresented in medicine to practice primary care in medically underserved communities in New York. This manuscript documents the experience of the CSOM in expanding global health education by introducing a new global health cancer training program, partnering with clinicians at the Ocean Road Cancer Institute (ORCI) in Tanzania. This manuscript illustrates the following points: (1) the CSOM curriculum that focuses on community health and social medicine; (2) the process by which students learn by developing research proposals for global cancer; (3) the field research experience and lessons learned; (4) learning about cancer and medicine in a developing country; and (5) lessons learned for translation from global to domestic underserved populations. We also suggest a checklist for future students interested in pursuing global cancer education and research, and recommendations for maximizing learning and career development of students interested in global cancer research and its application to underserved populations in the USA.

Developing Research Education Groups in African Cancer Centers: The Experience in Tanzania.

Research productivity and outcomes of junior researchers are usually correlated with the degree and quality of mentorship they receive. A bottom-up approach was followed to develop a research group at the Ocean Road Cancer Institute (ORCI), the major cancer center in Tanzania, to build upon the existing clinical and research resources and institutional global collaborations. The ORCI is a clinical center focused on radio- and chemo-therapy treatment of cancer patients from all over Tanzania. In addition, ORCI has a long-standing early detection program for educating women and screening them for cervical cancer. The ORCI physicians have been exposed to cancer research for the past 20 years through non-degree and degree training in the USA and Europe. In addition, US and European groups have been conducting collaborative research and training of oncologists and graduate students at ORCI. The exposure to research through the above-listed venues motivated the clinicians at ORCI to develop their own Research Club (RC) to learn about research methods, seek independent funding, and outline a research agenda for cancer research in Tanzania. However, it seems that mentorship is needed to help the RC members apply the lessons learned from didactic teaching. Mentorship is also needed to enable the RC members to utilize the enormous clinical and epidemiologic data generated by the institutional programs for prevention, treatment, and follow up of patients. This manuscript describes the inception of the program and its achievements, limitations, and suggested opportunities for improvement as a possible model for other LMICs.

Downstaging of cervical cancer in Tanzania over a 16-year period.

Globally, the highest cervical cancer mortality rates are found in East Africa. Visual inspection with acetic acid (VIA)-based screening in resource-poor settings has been shown to decrease the proportion of women presenting with late-stage cervical cancer, a process known as clinical downstaging. The only cancer treatment center in Tanzania, Ocean Road Cancer Institute (ORCI) in Dar es Salaam, opened a VIA-based cervical cancer screening program in 2002. We reviewed 6,676 medical records of cervical cancer patients at the ORCI from 2002-2011 to 2014-2018 for stage at diagnosis and screening status, among other variables. We investigated whether clinical downstaging occurred in this period among women screened at the ORCI, when compared to unscreened women. Our results indicated that the proportion of women presenting with late-stage cervical cancer among women screened at the ORCI decreased by 27.7% over the 16-year period (χ2 = 16.99; p = 0.0002). Among unscreened women, a non-significant 13.2% decrease in late-stage disease was observed (χ2 = 1.74; p = 0.4179). Our results suggest clinical downstaging occurred among women screened at the ORCI over the 16-year period, and this difference may be attributed to the screening program as the same decrease in stage was not observed among unscreened women during the same time period. At present, less than one percent of Tanzanian women receive yearly cervical cancer screenings. Access to screening through expansion of the ORCI screening clinic and the creation of more clinics should be prioritized.

Using Key Informants to Evaluate Barriers to Education and Acceptability of the HPV Vaccine in Tanzania: Implications for Cancer Education.

Cervical cancer is the third most common cancer globally, with high mortality when left untreated. In sub-Saharan Africa, Tanzania shows higher incidence rates of cervical cancer at 59.1 per 100,000 compared with the global average of 13.1 per 100,000. The HPV vaccine has been shown to successfully reduce HPV infection and is recommended for school-age girls and boys in the USA. Understanding the acceptability of the HPV vaccine and the barriers to vaccination is important for ensuring that HPV vaccination programs are successful. In 2016, Tanzania began school-based HPV vaccination programs in cities and towns surrounding Dar es Salaam, the largest city in Tanzania. Successful implementation of HPV vaccination programs in Dar es Salaam relies on overcoming barriers to vaccination. This study focused on primary school teachers as key informants to assess these barriers. Participants were given a short survey and then asked to participate in focus group sessions. Overall, knowledge of HPV was low, with only 37% of participants having heard of the HPV and only 28.6% having heard of the HPV vaccine. Teachers had a very positive response to the HPV educational sessions. Of the teachers who completed the questionnaires, 100% of them were willing to speak with their school parents about the HPV vaccine and 99% would recommend this vaccine to parents. This study has significant implications for national cancer prevention vaccination programs, not only in Tanzania, but also in other countries starting HPV vaccination as teachers are potentially important advocates for immunization and other childhood health initiatives.

Factors related to completion of referral among women with suspected cervical cancer and dysplasia in Tanzania.

OBJECTIVE: To investigate completion of referral among women with suspected cervical cancer in Tanzania. METHODS: Retrospective cohort study of 196 women referred from two healthcare clinics to Ocean Road Cancer Institute, Dar es Salaam, between March 2016 and June 2018. Women with precancerous lesions or suspected cancer were interviewed about their knowledge and perception of cervical cancer and referred for follow-up. RESULTS: Most participants were unable to name symptoms (55.1%), prevention methods (88.3%), or treatments (59.0%), although 79.1% rated the disease as severe. Women who came for routine early detection were less likely to complete referral than those who did not (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.05-0.70). Women who knew someone who died from cervical cancer were 5.40 times more likely to complete referral than those who did not. Knowing someone with cervical cancer was a predictor of referral completion in three multivariate models: OR, 5.62 (95% CI, 2.20-14.38); 4.34 (1.64-11.47); and 4.61 (1.72-12.36). Having severe symptoms was a predictor of non-completion in two models: 0.30 (0.12-0.75) and 0.35 (0.14-0.87). CONCLUSION: Patient-directed interventions should include education involving survivors of cancer and dysplasia, whereas system-directed interventions should utilize reminders to increase referral completion.

Quantifying the under-estimation of cervical Cancer in remote regions of Tanzania.

BACKGROUND: Cervical cancer is the most common cancer among women in Sub-Saharan countries, including Tanzania. While early detection and diagnosis are available in some parts of this large country, radiotherapy has been only available at the Ocean Road Cancer Institute (ORCI), in the capital city of Dar es Salaam and is just starting in a few regions. METHODS: The objective of this study was to compare the observed incidence of cervical cancer for the two remote regions of Mwanza in western Tanzania and Mbeya in southern Tanzania, based on their patients treated at the ORCI from 2011 to 2014. RESULTS: The number patients referred and treated at ORCI were (120 from Mwanza, and 171 from Mbeya, representing 24.6 and 32.8% of the patients histopathologically confirmed in the two sites, respectively. The results showed significant underestimation of cervical cancer in the two regions. The vast majority of patients who were histopathologically-confirmed in their local regions (73.92% from Mwanza and 65.1% from Mbeya), but did not receive the needed radiotherapy treatment at the ORCI. The estimated incidence for the two regions based on the number of patients treated at the ORCI were underestimated by 53.9% for Mwanza and 68.9% for Mbeya. CONCLUSIONS: Local establishment of radiotherapy treatment facilities in remote regions in Tanzania and similar other low-income countries is essential for providing effective treatment and improving survival of diagnosed cervical cancer patients. Linkage between the records of local remote hospitals and the main cancer treatment center in the capital city can also help support the emerging the population-based cancer registry at ORCI.

Comprehensive Cervical Cancer Prevention in Tanzania (CONCEPT) study: Cohort profile.

PURPOSE: Cervical cancer is a major cause of death among women in Eastern Africa, and the distribution of human papillomavirus (HPV) according to HIV status is inadequately characterised in this region. In order to guide future cervical cancer preventive strategies that involve HPV testing, the Comprehensive Cervical Cancer Prevention in Tanzania (CONCEPT) study was established in 2015. The CONCEPT cohort aims to investigate the natural history of HPV and determine acquisition and persistence patterns of high-risk (HR) HPV among HIV-positive and HIV-negative women. Further, the influence of lifestyle and sexual/reproductive factors will be investigated. The main objective of this article is to describe how the CONCEPT cohort was established. PARTICIPANTS: Women aged 25-60 years were enrolled from cervical cancer screening clinics in Dar-es-Salaam and Moshi, Tanzania. Data were collected at baseline, at 14 months (first follow-up) and at 28 months (second follow-up). Biological samples included two cervical swabs for careHPV DNA testing, cytology, Hybrid Capture 2, genotyping and blood samples for HIV. Visual inspection with acetic acid was performed, and sociodemographic, lifestyle and sexual/reproductive characteristics were collected through a standardised questionnaire. FINDINGS TO DATE: 4043 women were included in the cohort from August 2015 to May 2017. At baseline, 696 (17.1%) women were HR HPV positive, and among these, 31.6% were HIV positive; 139 women (3.4%) had high-grade squamous intraepithelial lesions. 3074 women (81%) attended the first follow-up. The majority attended after receiving a phone call reminder (35%) or from home via self-samples (41%). At first follow-up, 438 (14.4%) were HR HPV positive and 30.4% of these were HIV positive. FUTURE PLANS: A second follow-up is underway (17 December 2018-October 2020). We plan to integrate our data with a previous cross-sectional HPV study from Tanzania to increase the power of our findings. Researchers interested in collaborating are welcomed, either by extracting data or jointly requesting further investigation from the cohort.

Reproducibility of a Rapid Human Papillomavirus Test at Different Levels of the Healthcare System in Tanzania: The AISHA Study.

BACKGROUND: To inform policy makers in Tanzania if and how best to implement rapid HPV testing, we assessed the interobserver reproducibility of careHPV test at three different levels of the healthcare system in an urban and a rural region of Tanzania. METHODS: Women aged 30 to 50 years were screened by careHPV testing in two primary healthcare centers (PHC), two district hospitals (DiH), and two regional hospitals (ReH). Aliquots were retested at regional (ReH) and national referral laboratories (NRL). Reproducibility was evaluated using agreement and kappa index measures. Intralaboratory reproducibility was also evaluated in a set of 10 positive and 10 negative samples. RESULTS: Samples from 1,134 women were locally tested and retested at ReH and/or NRL. Test results from Dar es Salaam ReH and Kilimanjaro PHC showed clear quality problems including suspicion of contamination during testing or aliquoting. After excluding these samples, 18.8% of 743 women were HPV positive at clinic level. The resulting careHPV reproducibility at different levels of the healthcare system was very good [agreement 95.7%, 95% confidence interval (CI), 94.0-96.9; kappa, 0.86, 95% CI, 0.81-0.91]. Intralaboratory agreement was also very good across four different experiments, with Fleiss' kappa between 0.87 (95% CI, 0.61-1.00) and 1.00 (0.75-1.00). CONCLUSIONS: Rapid HPV testing was highly reproducible between lower and higher levels of the healthcare system in Tanzania; however, performance seems to be operator dependent. IMPACT: The careHPV test seems to be a feasible option for cervical cancer screening in an organized, decentralized system and in limited-resource settings if quality assurance measures are in place.

Mycoplasma Co-Infection Is Associated with Cervical Cancer Risk.

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae. To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., and Lactobacillus iners. A subset of 134 women were used for 16s metagenomic sequencing of cervical DNA to establish the relative abundance of Mycoplasmataceae and Lactobacillus present. PCR detection of bacteria at the cervix found Ureaplasma spp. in 51.4% of women, M. hominis in 34%, M. genitalium in 2.3%, and L. iners in 75.6%. M. hominis and M. genitalium infection were significantly more prevalent among women with HPV and HIV. M. hominis prevalence was similar despite severity of cervical lesions; however, abundance of M. hominis increased significantly in women with cervical lesions. These results emphasize the importance of understanding the relationship between M. hominis and HPV-related cervical pathogenesis.

How the Cervical Microbiota Contributes to Cervical Cancer Risk in Sub-Saharan Africa.

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because population statistics are not available for the region, estimates are derived from smaller cohort studies. Microbiota associated with cervical inflammation have been found to be especially prevalent in sub-Saharan Africa, and to associate with increased cervical cancer risk. In addition to high prevalence and diversity of HIV and HPV, intracellular bacterial infections such as Chlamydia, Gonorrhea, and Mycoplasma hominis are much more common than in regions with a low burden of cervical cancer. This suggests the prevalence of cervical cancer in sub-Saharan Africa may be partially attributed to increased cervical inflammation resulting from higher likelihood of cervical infection and/or microbial dysbiosis.

Impact of Initiating Screening Programs on Referral and Management of Cervical Cancer in Tanzania.

PURPOSE: We investigated the impact of screening rural patients on referral and management of cervical cancer in Tanzania. METHODS: After reviewing more than 10,000 medical records of patients with cervical cancer who visited Ocean Road Cancer Institute (ORCI) from 2005 to 2014, 108 patients were from the rural communities of Bagamoyo and Chalinze. We abstracted demographic, clinical, and lifestyle factors and linked the data set to databases of all 1,151 patients who visited the Bagamoyo screening clinic from 2011 to 2014 and 1,273 patients who visited the Chalinze screening clinic from 2012 to 2014. RESULTS: After initiation of the rural screening clinics, difference in duration from diagnosis to prescribed treatment increased from 50.5 to 88 days (P = .030), and duration from referral to treatment increased from 38.6 to 101.3 days (P = .041). Proportion of patients who received combination chemoradiotherapy increased from 34.3% to 69% (P = .001) and completion of treatment decreased from 94.4% to 72.41% (P = .002) after initiation of the ORCI screening clinic. Patients who visited Muhimbili National Hospital had significantly shorter periods between referral and prescribed treatment than patients who did not use the Muhimbili National Hospital (mean ± standard deviation, 49.4 ± 128.8 and 112.1 ± 195.31 days, respectively; P = .010). Patients who were treated at ORCI had significantly shorter periods between diagnosis and referral to treatment (mean ± standard deviation, 31.4 ± 62.35 and 36.4 ± 121.79 days, respectively; P = .005). CONCLUSION: Future research should focus on investigating barriers to seeking cancer care, benefits of chemoradiotherapy in this population considering the change in prescribed treatment, and time until diagnosis and treatment. Prescription of complex treatments that require more visits to treatment centers may also contribute to decline in completion of treatment.

Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions.

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals.IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.

Needs for Professional Education to Optimize Cervical Cancer Screenings in Low-Income Countries: a Case Study from Tanzania.

Cervical cancer is a significant health problem in many developing countries. Due to limited treatment facilities for cancer in Tanzania, a screening referral program was developed between two urban clinics and Ocean Road Cancer Institute (ORCI), the only cancer treatment center in Tanzania. This study aimed to evaluate the effectiveness of the program and to identify opportunities for professional education. The study included 139 patients who were referred to ORCI from the screening clinics of Magomeni and Temeke between January 2015 and May 2016. Abstracted data from the medical records included patient age, screening results, and treatment. Eight nurses performing screening at the three locations were interviewed about their screening experience. Over half of the referrals (51.9%) were false positives. False positive diagnosis was more common among younger patients (35.68 ± 8.6 years) (p < 0.001) and those referred from Magomeni (59.8%) (p < 0.01) than referrals of older patients (42.46 ± 11.1 years) or those from Temeke (33.3%). Interviews of nurses showed differences among clinics, including resources, experience, and documentation of screening results. The high false positive rates and the variation of accuracy of screening between the two clinics showed a need for professional education of nurses and improvement in the health systems. Continuous education of nurses may increase the effectiveness of cervical screening. Health system enhancement of screening facilities such as provision of Lugol's iodine, more space for screening, and consistency and completion of screening records are needed to increase the accuracy of cervical screening and referrals in Tanzania and other similar low-income countries.

Factors associated with a cervical high-grade lesion on cytology or a positive visual inspection with acetic acid among more than 3300 Tanzanian women.

OBJECTIVES: Cervical cancer screening by visual inspection with acetic acid (VIA) is a widely used alternative to cytology in developing countries. This study aimed to evaluate risk factors associated with a positive VIA test and with cervical high-grade lesions on cytology. METHODS: We conducted a large cross-sectional study among 3339 women from urban and rural Tanzania. Study participants were interviewed about socio-demographic, reproductive and lifestyle factors. Blood samples were tested for HIV, and a gynaecological examination was performed. Human papillomavirus (HPV) status was determined by Hybrid Capture 2, and HPV genotyping was done using the LiPA Extra test. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and confidence intervals (CIs). RESULTS: The strongest risk factors for VIA positivity were positivity to HIV (OR = 3.48; 95% CI: 2.34-5.17) or to high-risk HPV (HrHPV) (OR = 1.97; 95% CI: 1.37-2.85). HrHPV was by far the strongest predictor of high-grade cytology (OR = 110.1; 95% CI: 50.4-240.4), while there was no significant association with HIV in the multivariable analysis (OR = 1.27; 95% CI: 0.78-2.08). After adjustment for HrHPV, HIV and age, the risk of high-grade cytology also increased with increasing age, number of births and low body mass index (BMI), while high BMI decreased the risk of VIA positivity. CONCLUSIONS: Infection with HrHPV is a major risk factor for high-grade cytology, while VIA positivity is associated with HIV and to a lesser extent with HrHPV.

Analytical performance of a low-cost multiplex polymerase chain reaction human papillomavirus genotyping assay for use in Sub-Saharan Africa.

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low-cost HPV detection in Sub-Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high-risk and two low-risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra-laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by comparison with the widely accepted and validated HPV My09/My11 amplification and hybridization assay. Statistics; the Cohen kappa (κ) and McNemar P values were used to analyze interobserver and intermethod agreement. Overall concordance between the multiplex and line blot hybridization assays was 99% (per sample) with a κ value equal to 0.95; and 96.49% (per detection event) with a κ value of 0.92. Interobserver reproducibility of the assay per sample was 95.76% with κ of 0.91. These results demonstrate that the multiplex HPV PCR assay has high analytical sensitivity and specificity in detecting as many as 16 different HPV genotypes and that its simplicity and low cost makes it well suited for sub-Saharan Africa.