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.

Persistence and risk factors of high-risk human papillomavirus infection among HIV positive and HIV negative tanzanian women: a cohort study.

BACKGROUND: High-risk (HR) human papillomavirus (HPV) persistence is the most important risk factor for cervical cancer. We have assessed the type-specific HR HPV persistence among HIV positive and HIV negative Tanzanian women and factors associated with HR HPV persistence. METHODS: In a cohort study including 4080 Tanzanian women, 3074 attended follow-up examination (up to 32 months after enrollment). Cervical samples were obtained for liquid-based cytology and HPV DNA testing using Hybrid Capture 2 and Inno-Lipa Extra II. Information on lifestyle factors was collected through a personal interview. The probability of HR HPV persistence at a given time point since enrollment was estimated non-parametrically using the EMICM algorithm. RESULTS: Among the 462 women HR HPV positive at enrollment, 158 had at least one identical type detected at follow-up. The probability of persistence at 18 months after enrollment was 34.2 (95% CI 29.0-39.4). Stratifying by HIV status, the persistence probability was 42.9% (95% CI 33.5-51.9) among HIV positive, and 28.0% (95% CI 22.1-34.2) among HIV negative. Overall, HR HPV persistence was most common for HPV58, 35, 16, 31, and 52. Among HIV positive women it was HPV45, and HPV16, followed by HPV58 and HPV18, and among HIV negative women it was HPV31, HPV33 and HPV58. Risk factors associated with persistence of HR HPV were older age, longer interval between enrollment and follow-up, binge drinking, and HIV status. CONCLUSIONS: HR HPV persistence was common in Tanzania, and most common among HIV positive women. Overall, persistence was most frequent for HPV 58, 35, 16, 31 and 52. The nonavalent HPV vaccine should be considered.

Incident detection of human papillomavirus - a prospective follow-up study among Tanzanian women with a focus on HIV status.

BACKGROUND: The causative role of human papillomavirus (HPV) in cervical carcinogenesis is well established; however, prospective studies examining high-risk(HR)-HPV acquisition among adult women in HIV-prevalent settings are limited. METHODS: We conducted a prospective study among women (25-60 years) attending cervical cancer screening in Tanzania. Cervical specimens obtained at enrolment and follow-up were tested for HPV. Participants were interviewed on lifestyle and tested for HIV. RESULTS: Among 3805 eligible women, 3074 (80.8%) attended follow-up (median time between the 2 examinations, 17.3 months); 307 had missing HPV results at enrolment or follow-up, leaving 2767 study participants. Among 2253 women initially HR-HPV negative, 184 acquired HR-HPV-incidence: 54.5 per 1000 person-years (95% CI:47.1-62.9); among HIV-positive women 75.2 per 1000 person-years (95% CI:54.5-103.7), HIV-negative 50.9 per 1000 person-years (95% CI:43.3-60.0). HPV52 and HPV16 were the most frequently acquired types. In multivariable regression analysis, HIV positivity, low CD4 count, younger age, and multiple sexual partners were associated with increased odds of HPV acquisition. CONCLUSION: HPV acquisition was higher among HIV-positive than HIV-negative women, especially women with low CD4 counts. Improvement of immune status among HIV-positives may decrease HPV acquisition. Nonavalent HPV vaccination should be considered given the pattern of HR-HPV types acquired.

Acceptability and feasibility of self-sampling and follow-up attendance after text message delivery of human papillomavirus results: A cross-sectional study nested in a cohort in rural Tanzania.

INTRODUCTION: The objective was to determine if self-collection of vaginal samples for human papillomavirus (HPV) testing was acceptable and feasible in rural Tanzania and to assess the extent of attendance at a follow-up appointment among women who tested HPV-positive after delivery of HPV results via text messages. MATERIAL AND METHODS: A combined cross-sectional and cohort study was conducted among women aged 25-60 years from rural Kilimanjaro, Tanzania. Women were offered HPV self-sampling or traditional visual inspection of the cervix with acetic acid. If HPV self-sampling was preferred, participants received instructions on self-collection with an Evalyn Brush. A questionnaire was used to assess the acceptability and feasibility of the self-sampling procedure for the participants and delivery of HPV results via text messages. A mobile text message platform was used to send private text messages with the screening results to the participants. RESULTS: A total of 1108 women were enrolled and self-collected an HPV sample; 11.8% tested positive for high-risk HPV. The majority (98.9%) agreed that they had no trouble in understanding the instructions on how to perform the self-collection and that they would recommend it to a friend (94.5%) or as a standard screening method in Tanzania (95.5%). A minority of women experienced bleeding (2.4%) or pain (6%) while collecting the sample, while some were worried that they would get hurt (12.7%) or felt embarrassed (3.5%). The majority (98.4%) of women would like to receive the screening test results via text messages. Eighty-two per cent of those who tested positive for high-risk HPV attended the follow-up appointment after receiving a text message reminder and an additional 16% attended after receiving both a text message and a phone call reminder whereas 2% did not attend follow up at all. Attendance was not influenced by age, marital status, education level, parity, or HIV status. CONCLUSIONS: Human papillomavirus self-sampling and text-message feedback delivery are generally well-perceived and accepted among rural Tanzanian women, and the majority of HPV-positive women attended a follow-up appointment after receiving their HPV results and follow-up appointment via text messages. This screening method may have potential to be transferrable to other low-income countries with a high incidence of cervical cancer and so improve cervical cancer screening attendances.

Effectiveness of One-Way Text Messaging on Attendance to Follow-Up Cervical Cancer Screening Among Human Papillomavirus-Positive Tanzanian Women (Connected2Care): Parallel-Group Randomized Controlled Trial.

BACKGROUND: Rapid human papillomavirus (HPV) DNA testing is an emerging cervical cancer screening strategy in resource-limited countries, yet it requires follow-up of women who test HPV positive. OBJECTIVE: This study aimed to determine if one-way text messages improved attendance to a 14-month follow-up cervical cancer screening among HPV-positive women. METHODS: This multicenter, parallel-group randomized controlled trial was conducted at 3 hospitals in Tanzania. Eligible participants were aged between 25 and 60 years, had tested positive to a rapid HPV test during a patient-initiated screening, had been informed of their HPV result, and had a private mobile phone with a valid number. Participants were randomly assigned in a 1:1 ratio to the intervention or control group through an incorporated algorithm in the text message system. The intervention group received one-way text messages, and the control group received no text messages. The primary outcome was attendance at a 14-month health provider-initiated follow-up screening. Participants were not blinded, but outcome assessors were. The analysis was based on intention to treat. RESULTS: Between August 2015 and July 2017, 4080 women were screened for cervical cancer, of which 705 were included in this trial-358 women were allocated to the intervention group, and 347 women were allocated to the control group. Moreover, 16 women were excluded before the analysis because they developed cervical cancer or died (8 from each group). In the intervention group, 24.0% (84/350) women attended their follow-up screening, and in the control group, 23.8% (80/335) women attended their follow-up screening (risk ratio 1.02, 95% CI 0.79-1.33). CONCLUSIONS: Attendance to a health provider-initiated follow-up cervical cancer screening among HPV-positive women was strikingly low, and one-way text messages did not improve the attendance rate. Implementation of rapid HPV testing as a primary screening method at the clinic level entails the challenge of ensuring a proper follow-up of women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02509702; https://clinicaltrials.gov/ct2/show/NCT02509702. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10.2196/15863.

"The best thing is that you are doing it for yourself" - perspectives on acceptability and feasibility of HPV self-sampling among cervical cancer screening clients in Tanzania: a qualitative pilot study.

BACKGROUND: Cervical cancer is the most common type of cancer in sub-Saharan Africa, and it is also the cancer disease that most women die from. The high mortality rate is partly due to low attendance rates to screening services and low sensitivity of visual inspection with acetic acid, which is the standard screening method used in screening programs in sub-Saharan Africa. In order to overcome of the burden of disease new screening strategies and methods are warranted. This study aims to explore the acceptability and feasibility of HPV self-sampling compared to provider-based sampling among cervical cancer screening clients living in Dar es Salaam. METHODS: Women attending cervical cancer screening at Ocean Road Cancer Institute in Dar es Salaam, Tanzania between February - April 2017 were invited into the study. The participants had (1) a provider-collected sample, and (2) a self-sample for HPV on top of the regular cervical cancer screening. 50% of the participants conducted the self-sample after receiving a written instruction guide of how to collect the sample (written). The other 50% received both the written and an oral introduction to self-sampling (written+). All participants could ask for nurse assistance during self-sample collection if needed. Individual semi-structured interviews were conducted with the participants post sample collection. Data collection stopped when saturation was reached. Data were analysed using a thematic content analysis. RESULTS: Twenty-one women participated in the study. Regardless of how women were introduced to the self-sample (written or written+), there was a high demand for nurse presence as they felt uncertain of their personal capabilities to collect the self-sample correctly. However, as long as nurse assistance was an option most women perceived self-sampling as easy and comfortable though few experienced bleeding and pain. The majority of women preferred self-sampling over provider-sampling primarily due to the method being more private than the provider-sampling. CONCLUSIONS: HPV self-sampling was well-perceived and accepted, however, for the method to be feasible a nurse needed to be present. HPV Self-sampling may be an alternative method to increase uptake of cervical cancer screening. Larger quantitative studies are recommended to support the study findings.

Text messages to increase attendance to follow-up cervical cancer screening appointments among HPV-positive Tanzanian women (Connected2Care): study protocol for a randomised controlled trial.

BACKGROUND: Cervical cancer is a major health concern in Tanzania, caused by poor attendance for cervical cancer screening and follow-up of women at risk. Mobile telephone health interventions are proven effective tools to improve health behaviour in African countries. So far, no knowledge exists on how such interventions may perform in relation to cervical cancer screening in low-income settings. This study aims to assess the degree to which a Short Message Service (SMS) intervention can increase attendance at appointments among women who have tested positive for high-risk (HR) Human Papillomavirus (HPV) during cervical cancer screening. METHODS/DESIGN: Connected2Care is a non-blinded, multicentre, parallel-group, randomised controlled trial. Tanzanian women testing positive to HR HPV at inclusion are randomly assigned in an allocation ratio of 1:1 to the SMS intervention or the control group (standard care). In a period of 10 months, the intervention group will receive 15 one-directional health educative text messages and SMS reminders for their appointment. The total sample size will be 700 with 350 women in each study arm. Primary outcome is attendance rate for follow-up. Secondary objectives are cost-effectiveness, measured through incremental ratios, and knowledge of cervical cancer by a 16-item true/false scale questionnaire at baseline and follow-up. Barriers against implementing the intervention will be assessed in a mixed-methods sub-population study. DISCUSSION: This study may provide information on the potential effects, costs, and barriers in implementing an SMS intervention targeting a group of women who are followed up after testing positive for HR HPV and are, therefore, at increased risk of developing cervical cancer. This can guide decision-makers on the effective use of mobile technology in a low-income setting. Trial status: recruiting. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02509702 . Registered on 15 June 2015.