Cervical Cancer Screening Strategies Research Articles

Estimated Quality of Life and Economic Outcomes Associated With 12 Cervical Cancer Screening Strategies

Many cervical cancer screening strategies are now recommended in the United States, but the benefits, harms, and costs of each option are unclear. To estimate the cost-effectiveness of 12 cervical cancer screening strategies. The cross-sectional portion of this study enrolled a convenience sample of 451 English-speaking or Spanish-speaking women aged 21 to 65 years from September 22, 2014, to June 16, 2016, identified at women's health clinics in San Francisco. In this group, utilities (preferences) were measured for 23 cervical cancer screening-associated health states and were applied to a decision model of type-specific high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. Test accuracy estimates were abstracted from systematic reviews. The evaluated strategies were cytologic testing every 3 years for women aged 21 to 65 years with either repeat cytologic testing in 1 year or immediate hrHPV triage for atypical squamous cells of undetermined significance (ASC-US), cytologic testing every 3 years for women age 21 to 29 years followed by cytologic testing plus hrHPV testing (cotesting), or primary hrHPV testing alone for women aged 30 to 65 years. Screening frequency, abnormal test result management, and the age to switch from cytologic testing to hrHPV testing (25 or 30 years) were varied. Analyses were conducted from both the societal and health care sector perspectives. Utilities for 23 cervical cancer screening-associated health states (cross-sectional study) and quality-adjusted life-years (QALYs) and total costs for each strategy. Utilities were measured in a sociodemographically diverse group of 451 women (mean [SD] age, 38.2 [10.7] years; 258 nonwhite [57.2%]). Cytologic testing every 3 years with repeat cytologic testing for ASC-US yielded the most lifetime QALYs and conferred more QALYs at higher costs ($2166 per QALY) than the lowest-cost strategy (cytologic testing every 3 years with hrHPV triage of ASC-US). All cytologic testing plus hrHPV testing (cotesting) and primary hrHPV testing strategies provided fewer QALYs at higher costs. Adding indirect costs did not change the conclusions. In sensitivity analyses, hrHPV testing every 5 years with genotyping triage beginning at age 30 years was the lowest-cost strategy when hrHPV test sensitivity was markedly higher than cytologic test sensitivity or when hrHPV test cost was equated to the lowest reported cytologic test cost ($14). Cytologic testing every 3 years for women aged 21 to 29 years with either continued cytologic testing every 3 years or switching to a low-cost hrHPV test every 5 years confers a reasonable balance of benefits, harms, and costs. Comparative modeling is needed to confirm the association of these novel utilities with cost-effectiveness.

Acceptability of Human Papillomavirus Self-Sampling Among a National Sample of Women in the United States.

As human papillomavirus (HPV) self-sampling continues to emerge as a potential cervical cancer screening strategy in the United States, it is necessary to examine women's acceptability of this screening approach. Furthermore, since several HPV self-sampling devices exist, it is important to determine if women's preferences differ by device type. We conducted an online survey in Fall 2017 with a national sample of women (n = 605) ages 21–65 years (the recommended age range for cervical cancer screening). Multivariable linear regression identified correlates of women's willingness to use an HPV self-sample at home. We used repeated measures analysis of variance to determine if preferences differed across four self-sampling devices: Evalyn® Brush (Device A), HerSwab® (Device B), Catch-All® Swab (Device C), and Qvintip® (Device D). Most women were willing to use an HPV self-sample at home (mean = 4.03 [possible range: 1–5], standard deviation = 1.09, 72.7% indicated “probably willing” or “definitely willing”). The most common concerns about self-sampling were related to test accuracy (53.1%) and obtaining the sample incorrectly (51.1%). Women were more willing to use an HPV self-sample at home if they reported greater perceived severity of cervical cancer (β = 0.16), reported an annual income less than $50,000 (β = 0.13), or were a former smoker (β = 0.11). Women were more willing to use Device A (mean = 3.72, 67.6% indicated “agree” or “strongly agree”), Device C (mean = 3.86, 73.9% indicated “agree” or “strongly agree”), and Device D (mean = 3.81, 72.1% indicated “agree” or “strongly agree”) than Device B (mean = 3.36, 49.4% indicated “agree” or “strongly agree”; all p < 0.05). Acceptability of HPV self-sampling as a cervical cancer screening strategy is generally high among women. Future efforts should consider the potential impact that device type may have on women's use of an HPV self-sample at home.

Massive single visit cervical pre-cancer and cancer screening in eastern Democratic Republic of Congo

BackgroundIn the Democratic Republic of Congo (DRC), practical and affordable strategies for cervical cancer screening are needed to detect and treat pre-cancerous and cancerous lesions in a timely fashion. This study presents the results of mass cervical cancer screenings in eastern DRC using a “screen and treat” approach.MethodsIn two mass cervical cancer screening campaigns, patients underwent a combination of visual inspection of the cervix with acetic acid, visual inspection of the cervix with Lugol iodine solution, and colposcopy with or without loop electrosurgical excision procedure. Cervical biopsy samples were taken for histology analysis. Marital status, age, history of abnormal bleeding, and number of pregnancies were recorded for each patient and association analyses were performed.ResultsOf the 644 women who received cervical pre-cancer and cancer screening, 48 had suspicious pre-cancer and cancer lesions that were biopsied (7.45%). On histology analysis cervical intraepithelial neoplasia (CIN) was identified in 15 (2.33%), squamous cell carcinoma (SCC) was identified in 6 (0.93%) and non-neoplastic cervicitis was identified in 11 (1.71%). Abnormal bleeding was significantly associated with CIN/SCC but no significant association was observed for prior pregnancy, patients’ home region, or age.ConclusionForty-eight women with suspicious pre-cancerous or cancerous lesions were successfully identified using the “screen and treat” approach in eastern DRC, suggesting that this approach is feasible for reducing cervical cancer morbidity and mortality. However, community awareness would be necessary, providers would have to be properly trained, referral and follow up mechanisms would have to be put in place, and equipment / supplies would have to be secured if the “screen and treat” approach is to be successful on a wider scale. There is ongoing need for HPV vaccination in DRC as a primary prevention strategy against cervical cancer.

Results of a Pilot Study of a Mail-Based Human Papillomavirus Self-Testing Program for Underscreened Women From Appalachian Ohio.

Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet few mail-based HPV self-testing programs have been implemented in the United States. We report the results of a pilot study of a mail-based program, the Health Outcomes through Motivation and Education Project. In 2015 to 2016, we recruited 103 women from Appalachian Ohio who were aged 30 to 65 years and had not received a Papanicolaou (Pap) test in at least 3 years. Women were mailed an HPV self-test and randomized to receive either (a) self-test instructions developed by the device manufacturer and a standard information brochure about cervical cancer (control group) or (b) self-test instructions developed by the Health Outcomes through Motivation and Education Project and a photo story information brochure about cervical cancer (intervention group). Logistic regression compared study arms on HPV self-test return and receipt of a Pap test. Overall, 80 (78%) women returned their HPV self-test. Return was similar among the intervention and control groups (78% vs. 77%; odds ratio, 1.09; 95% confidence interval, 0.43-2.76). Among returners, 26% had an oncogenic HPV type detected in their sample. Women who returned their self-test reported high levels of satisfaction and positive experiences with the self-testing process. Few women overall received a Pap test (11%), and Pap testing was similar among the intervention and control groups (14% vs. 8%; odds ratio, 1.91; 95% confidence interval, 0.52-6.97). Mail-based HPV self-testing programs are a potentially promising strategy for reaching underscreened women in Appalachia. Efforts are needed to better understand how to optimize the success of such programs.

Implementation of a Cervical Cancer Screening Strategy Using HPV Self-Sampling for Women Living in Rural Areas

Background: The implementation of population screening for cervical lesions in rural areas has been particularly challenging for a variety of reasons, including geographic isolation, limited access to medical care, lack of awareness of cancer risks, lower education levels, and embarrassment about having the clinical examination. Methods: This study was designed to evaluate the use of self-sampling for human papillomavirus (HPV) screening in the rural communities served by our hospital. To develop the study group, we trained a local police officer who was already interacting with the rural community to explain cancer risks and the ease of self-sampling to the women. Results: We identified a study group of 386 women, of whom 369 (95.6%) agreed to participate in the study. To test for high-risk HPV, we performed the Cobas PCR test, and of 340 valid samples, 45 (12.2%) were positive for at least 1 of the high-risk HPV subtypes. All positively tested women were referred for colposcopy and Papanicolaou testing. The follow-up biopsies showed that 40% had low-grade intraepithelial neoplasia (CIN1), 6.6% had high-grade intraepithelial neoplasia (CIN2/3), and 4.4% had squamous cell carcinoma. Conclusions: Self-collection for HPV testing by women living in isolated communities is highly efficient and has potential for cost-effective screening by taking advantage of existing support networks, such as the local police service.

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies

BackgroundPrimary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal.MethodsA budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25–64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2–3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer’s perspective.ResultsHPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (− 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (− 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years.ConclusionThe results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

Cost-effectiveness analysis of cervical cancer screening strategies in urban China

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions: Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

Global strategies for cervical cancer prevention and screening.

Cervical cancer is highly preventable and can be easily treated if detected at early stages. However there is disproportionate high burden of cervical cancer incidence and mortality in low-middle income (LMIC) country settings that lack organized screening and prevention programs. Robust evidence for prevention and screening of cervical cancer is currently available. However there are barriers for country specific adoption and implementation. These pose unique challenges such as organizing prevention and screening services delivery through the current health infrastructure, access to screening facilities, follow-up management and adequate linkages for confirmatory diagnosis and subsequent treatment. Overall cervical cancer screening rates and cancer screening among women still remains suboptimal in many LMIC's. Considering the complexities involved in organization, service uptake and delivery of population based cervical cancer prevention and screening programs, this article aims to provide evidence based appropriate, affordable and effective standardized cervical cancer prevention and screening guidelines that are operationally feasible to help adopt best practices for uniform adaptation and implementation leveraging with the existing public health care settings. Cost-effective strategies and tools to reduce cervical cancer burden worldwide to mitigate the existing disparities in cervical cancer burden between low-resourced and high-resourced settings are needed. The current cervical cancer prevention and screening guidelines are drawn from the most robust evidence generated from the randomised trials and cross-sectional studies undertaken in the socioeconomic, cultural and health systems context of varied geographic settings and therefore conform towards applicability for wide-scale, sustainable and uniform implementation of population based cervical cancer screening and prevention program.

Prevalence of oncogenic Human papillomavirus and genetic diversity in the L1 gene of HPV16 HPV 18 HPV31 and HPV33 found in women from Vojvodina Province Serbia

The main purpose of this paper is to estimate the pre-vaccination prevalence of 12 hrHPV types among 564 women from Vojvodina province (Serbia). The corrected contingency coefficient (Ccorr) was used to estimate the importance of association of examined HPV types and cytological diagnosis. The highest association with the abnormal cytology was observed for HPV 16 (Ccorr = 0.493) in all age groups of participants. The effect of HPV 16 was especially clear within the group of women older than 35 years (Ccorr = 0.691), compared with women younger than 35 (Ccorr = 0.333). The molecular characterization at the level of L1 gene of HPV 16, 18, 31 and 33 variants was for the first time assessed in our region. Nearly all HPV 16 isolates cluster with variant lineage A (96.4%) the remaining isolates clustering with variant lineage D. All of HPV 18 and HPV 33 isolates are clustering within the lineage A while isolates of HPV 31 group with lineages A and C. This contributes to understanding of intrinsic geographical and biological differences of examined HPV types and could be useful for development of cervical cancer screening strategies in Vojvodina (Serbia) and diagnosis of HPV related cervical cancer in general.

The distribution and prevalence of human papillomavirus in women in mainland China.

We conducted a systematic review of the epidemiology of high-risk human papillomavirus (HPV) infections in mainland Chinese women to provide a general profile for the application and subsequent effectiveness evaluation of HPV vaccines. The PubMed, Web of Science, Medline (Ovid), China National Knowledge Infrastructure, and Wanfang databases were used for the literature search. The epidemiological studies published from January 2000 to June 2018 on high-risk HPVs in mainland Chinese women were investigated to systematically evaluate their epidemiological status. A total of 198 eligible studies were included. The results of meta-analysis showed that the overall infection rate of high-risk HPVs in mainland Chinese women was 19.0% (95% confidence interval [CI], 17.1%-20.9%), and the top 5 subtypes with the highest infection rates were 16, 52, 58, 53, and 18. The overall infection rates of cervical intraepithelial neoplasia I (CINI), CINII+, and cervical cancer patients were 59.6% (95% CI, 52.7%-66.4%), 84.8% (95% CI, 81.2%-88.5%), and 89.9% (95% CI, 86.6%-93.1%), respectively. The high-risk HPV infections and common subtypes in women of various ages in various regions were different, and the high-risk HPVs and subtypes in cervical cancer patients in various regions were also different. In conclusion, we systematically analyzed the HPV infections in women who live on the Chinese mainland. The epidemiology of high-risk HPVs in mainland Chinese women is basically consistent with that for the rest of the world. The HPV vaccines currently licensed in China could cover the major prevalent high-risk HPV subtypes in China, providing a basis for the development of a cervical cancer screening strategy and vaccine implementation in China.

Cost-effectiveness evaluation of HPV self-testing offered to non-attendees in cervical cancer screening in Switzerland

ObjectiveAbout 30% of women who are eligible for cervical cancer (CC) screening remain un-screened or under-screened in Switzerland. HPV testing on self-collected vaginal samples (Self-HPV) has shown to be more sensitive than cytology while also reaching non-attendees. The objective of this study was to explore the cost-effectiveness of offering Self-HPV to non-attendees in Switzerland. MethodsA recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: Self-HPV and triage with colposcopy (Self-HPV/colpo), Self-HPV and triage with Pap cytology (Self-HPV/PAP), cytological screening and triage with HPV (PAP/HPV). Sensitivity analyses for the key parameters of the model were conducted to check the robustness of findings. ResultsOffering a Self-HPV screening to non-attendees could prevent 90% of CC and 94% of CC-related deaths in the study population. The current cytology-based program could reduce by 83% the number of CC cases and by 88% the number of CC-related deaths over the population's lifetime. Compared to the absence of screening, incremental cost-effectiveness ratios (ICER) were estimated to be, per saved Quality Adjusted Life Year (QALY), 12413US$ for the strategy Self-HPV/colpo, 11138US$ for the strategy Self-HPV/Pap and 22488US$ for the strategy PAP/HPV. ConclusionsOffering Self-HPV as a CC screening strategy to non-attendees in Switzerland is a cost-effective solution that is associated with a reduction of CC cases and related deaths. Self-HPV is more cost-effective than the currently used cytology-based screening.

A New Method for Cervical Cancer Screening? The Importance of Cervical Thickness on Ultrasound

Background: Cervical cytology and human papillomavirus (HPV) testing are the recommended screening strategies for cervical cancer. Ultrasound examination is used worldwide in patient management, especially in gynaecology. However, early detection of cervical carcinomas, especially cervical precancers, is usually difficult. We propose that in patients with cervical intraepithelial neoplasia (CIN), the thickness of the cervix increases with histological severity, and that this thickening can be detected by ultrasonography, both transabdominal sonography (TAS) and transvaginal sonography (TVS), which are the most common methods of evaluating pelvic symptoms. Our study aimed to test this hypothesis. Methods: Between February 2017 and April 2018, 12,019 women enrolled in the TVS group and 9096 women enrolled in the TAS group aged 20 years or older underwent cervical thickness measurement in the mid-sagittal plane. Based on histological diagnosis and image quality, 273 women in the TVS group and 212 women in the TAS group were ultimately eligible for analysis. The outcome was the cervical thickness associated with every CIN grade in each group. Findings: Cervical thickness increased with histological severity in both groups. In the TVS group, the cervical thickness was 22.53 mm for normal histology, 24.02 mm for CIN1, 24.79 mm for CIN2, 26.50 mm for CIN3 and 28.50 mm for cancer. The cervical thickness in the TAS group was 22.68 mm for normal histology, 24.55 mm for CIN1, 25.83 mm for CIN2, 27.00 mm for CIN3 and 30.81 mm for cancer. No difference in cervical thickness was found between the patients in the two groups with the same CIN grades. Interpretation: The thickness of the cervix increased with CIN grade, possibly demonstrating the potential for cervical cancer screening via ultrasound. However, further studies are required. Funding Statement: The authors state: None. Declaration of Interests: The authors state: None. Ethics Approval Statement: All the women participated in this study voluntarily and provided written informed consent before undergoing the ultrasound examination. The study was approved by the local ethics committee.

Fast approximate computation of cervical cancer screening outcomes by a deterministic multiple-type HPV progression model

Cervical cancer arises differentially from infections with up to 14 high-risk human papillomavirus (HPV) types, making model-based evaluations of cervical cancer screening strategies computationally heavy and structurally complex. Thus, with the high number of HPV types, microsimulation is typically used to investigate cervical cancer screening strategies. We developed a feasible deterministic model that integrates varying natural history of cervical cancer by the different high-risk HPV types with compressed mixture representations of the screened population, allowing for fast computation of screening interventions. To evaluate the method, we built a corresponding microsimulation model. The outcomes of the deterministic model were stable over different levels of compression and agreed with the microsimulation model for all disease states, screening outcomes, and levels of cancer incidence. The compression reduced the computation time more than 1000 fold when compared to microsimulation in a cohort of 1 million women. The compressed mixture representations enable the assessment of uncertainties surrounding the natural history of cervical cancer and screening decisions in a computationally undemanding way.

The human papillomavirus, cervical cancer and screening strategies: an update.

Cervical cancer, the most common gynaecological malignancy has been strongly correlated with the infection of human papillomavirus (HPV). Different risk factors exaggerate the onset and progression of cervical cancer to malignant and metastatic state. Recent outcomes for the identification of the molecular pathways involved in cervical cancer provide clues about novel bio or oncogenic markers that are proved to be helpful in monitoring the detection of lesion with a high risk of progression in cytological smears and histological specimens. Sexual health programs and public awareness with developing strategies is the ultimate requirement for combating cervical cancer worldwide. The current review discusses mechanism of HPV that links with cervical cancer, various risk factors for the progression of cervical pathologies including smoking, oral contraceptives and sexual factors as well as diagnostic and screening strategies for cervical cancer.

Economic evaluation of cervical cancer screening strategies in urban China.

ObjectiveThis study evaluated the feasibility of different cervical cancer screening strategies in urban China.MethodsA Markov model was constructed to simulate a hypothetical cohort of 100,000 females aged 30−59 years in a 20-year period. Screening strategies included liquid-based cytology (LBC) every three years, human papillomavirus (HPV) DNA testing every three and five years, respectively, and a combination of HPV DNA testing and LBC (HPV+LBC) every three and five years, respectively. Model outcomes included cumulative incidence over 20 years, cumulative risk of cervical cancer, costs, life year saved (LYS), quality-adjusted life years (QALYs) and benefits. The cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs), cost-utility ratios (CURs), and benefit-cost ratios (BCRs) were used as outcomes in the health economic evaluation analysis. Univariate sensitivity analyses were performed to examine the stability of the results.ResultsThe cumulative incidence of the five screening strategies ranged from 833.02 to 1,158.07 cases per 100,000 females. HPV DNA testing was most effective in reducing the cumulative risk of cervical cancer, saving life years and QALYs and gaining benefits. The CERs of HPV DNA testing every three and five years, and LBC every three years were considered to be very cost-effective if they were below China’s GDP per capita. The CERs of HPV+LBC were considered to be cost-effective if they were below three times GDP per capita. The incremental cost-effectiveness analysis showed that HPV DNA testing every three and five years, LBC every three years and HPV+LBC every five years were dominant strategies.ConclusionsThe findings of this study indicated that HPV DNA testing every five years or LBC every three years should be recommended in urban China.

Society of obstetrics and gynecology of Nigeria – Clinical practice guidelines: Guidelines for the prevention of cervical cancer

Clinical practice guidelines have been developed by professional societies globally. Each guideline although based on published scientific evidence reflected each country's socioeconomic peculiarities and unique medical environment. The Society of Obstetrics and Gynaecology of Nigerian has published guidelines in other clinical areas; however, this is the first edition of practice guidelines for the prevention of cervical cancer. The Guidelines Committee was established in 2015 and decided to develop the first edition of this guideline following Delphi pool conducted among members which selected cervical cancer prevention as the subject that guideline is urgently needed. These guidelines cover strategies for cervical cancer prevention, screening, and management of test results. The committee developed the draft guideline during a 2-day workshop with technical input from Cochrane Nigeria and Dr. Chris Maske, Lancet Laboratories, South Africa. The recommendations for each specific area were developed by the consensus, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the prevention of cervical cancer.

One-Way Text Messages versus No Text Messages on Attendance to Follow-Up Cervical Cancer Screening Among HPV-Positive Tanzanian Women (Connected2Care): A Parallel-Group Randomised Controlled Trial

Background: Rapid 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. We conducted a randomised controlled trial to determine if one-way text messages improved attendance to a 14-months follow-up cervical cancer screening among HPV-positive women. Methods: This multi-centre, parallel-group randomised controlled trial was conducted at three hospitals in Tanzania. Eligible participants were between 25-60 years, had tested positive to a rapid HPV-test during a patient-initiated screening, been informed of their HPV-result, and had a private mobile phone with a valid number. Participants were randomly assigned 1:1 into 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 to a 14-months health provider-initiated follow-up screening. Participants were not blinded but outcome assessors were. The analysis was intention-to-treat. Findings: Between August 2015 and July 2017, 4080 women were screened for cervical cancer of which 705 were included into this trial; 358 were allocated to the intervention group and 347 to the control group. Sixteen women were excluded prior to analysis due to developing cervical cancer or dying (eight from each group). In the intervention group, 84 women (24%) attended their follow-up screening, and in the control group 80 women (24%) attended (RR: 1·02; 95% CI: 0·79-1·33). Interpretation: 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 at clinic level in Tanzania entails a challenge of ensuring a proper follow-up of women. Trial Registration: ClinicalTrials.gov;NCT02509702; active, not recruiting. Funding Statement: The study is funded by the Danish International Development Agency (Danida; 14-P02-Tan/A26775) and the University of Southern Denmark (internal funds). Declaration of Interests: There are no competing interests for any of the authors. Ethics Approval Statement: The study protocol has been published elsewhere, and joined ethical approval for all study sites was obtained from the National Institute for Medical Research in Tanzania.

Cervical cancer screening research in the PROSPR I consortium: Rationale, methods and baseline findings from a US cohort.

Little is known about the effect of evolving risk-based cervical cancer screening and management guidelines on United States (US) clinical practice and patient outcomes. We describe the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium, methods and baseline findings from its cervical sites: Kaiser Permanente Washington, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Parkland Health & Hospital System/University of Texas Southwestern (Parkland-UTSW) and New Mexico HPV Pap Registry housed by University of New Mexico (UNM-NMHPVPR). Across these diverse healthcare settings, we collected data on human papillomavirus (HPV) vaccinations, screening tests/results, diagnostic and treatment procedures/results and cancer diagnoses on nearly 4.7 million women aged 18-89 years from 2010 to 2014. We calculated baseline (2012 for UNM-NMHPVPR; 2010 for other sites) frequencies for sociodemographics, cervical cancer risk factors and key screening process measures for each site's cohort. Healthcare delivery settings, cervical cancer screening strategy, race/ethnicity and insurance status varied among sites. The proportion of women receiving a Pap test during the baseline year was similar across sites (26.1-36.1%). Most high-risk HPV tests were performed either reflexively or as cotests, and utilization pattern varied by site. Prevalence of colposcopy or biopsy was higher at Parkland-UTSW (3.6%) than other sites (1.3-1.4%). Incident cervical cancer was rare. HPV vaccination among age-eligible women not already immunized was modest across sites (0.1-7.2%). Cervical PROSPR I makes available high-quality, multilevel, longitudinal screening process data from a large and diverse cohort of women to evaluate and improve the effectiveness of US cervical cancer screening delivery.

Risk stratification of type-specific human papillomavirus for cervical precancers: evidence from a cross-sectional study in Shenzhen

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P<0.05) and an analogous specificity (87.3% vs. 86.9%, P>0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone (P<0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference (P>0.05). Conclusions: Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.

Developing Interinstitutional Multimodality Model for Translational Studies for Cervical Cancer Screening and Treatment: Pragmatic Issues Pertaining to Logistics, Infrastructure and Solutions

Background and context: Cervical cancer claims the life of 67,500 women every year in India. Persistence of HPV leads to the development of high grade CIN which may progress to invasive cancer. Almost 80% of women are infected with the virus in their lifetime but only a small proportion of women progress to develop cervical cancer. In early cervical cancer patients despite surgery about 25% recur and in advanced cervical cancer about 50%-60% women respond to radiotherapy while the rest progress or recur with disease after standard treatment. The risk to progression and failure to treatment is dependent on both viral/tumor and host factors; therefore an integrated approach should be adopted in developing predictive and prognostic biomarkers to address these clinical questions. Aim: Establishing a clinical and translational research model to provide an infrastructure that will facilitate targeted screening and targeted therapeutics in cervical precancer and cancer. Strategy/Tactics: Integration of various premium institutions in the city with their infrastructure to form a “Systems Medicine Cluster” was established to conduct this research. We have adopted a primary HPV screening (HC2 DNA and genotyping) strategy as a clinical protocol and devised SOPS to enable sample collection strategies for several research usage from the same sample including cytology testing, genomics, metabolomics, microbiome, proteomics. Similarly a translational pathway has been created for seamless tissue collection from cancer patients for multidimensional research usage. Collaboration was established between clinicians, scientists, clinical trial coordinators, research nurses, data managers and biobank personnel to orchestrate this working model. Program/Policy process: Collaboration of various institutions to form a “Systems Medicine Cluster” to effectively implement research strategies for cervical cancer screening and treatment. Outcomes: With the help of translation work we intend to identify of viral and host factors which determine the persistence of the HPV in screened women, thereby risk stratifying them for colposcopic evaluation. In women with cervical cancer who are treated with standard care, we expect to identify modifiable tumor or host factors and drug targets that can be used to reduce the risk of recurrence and improve survival. In 3 months of implementation we have screened 260 women in the cervical cancer screening clinic and obtained samples from 190 cervical cancer patients for translational research. All women have also contributed to the collection of vaginal fluid and blood samples for various research protocols associated with cervical cancer. What was learned: These translational studies conducted hand in hand with clinical pathways requires meticulous planning and teamed approach. The formation of the “Systems Medicine Cluster” with different expertise to address clinical strategies has been a successful model.