Organized Cervical Cancer Screening Program Research Articles

Prevalence of high-risk human papillomavirus infection and cervical cytology abnormalities among women up to age 40 in the Tuzla Canton, Bosnia and Herzegovina

Cervical cancer is the second leading cause of female cancer in Bosnia and Herzegovina, and it is the most common female cancer in women 15 to 44 years old. Cervical cancer is etiologically associated with high-risk human papillomaviruses (HRHPV). Data on the prevalence of HRHPV in Bosnia and Herzegovina are scant. This study investigates the prevalence of HRHPV infection among women of reproductive age compared with cervical cytology in the Tuzla Canton. We analyzed the results of HRHPV testing and Papanicolaou (Pap) test results in women up to 40 years old diagnosed at the Tuzla University Clinical Center (UCC) from January 2019 to March 2020. Among 880 women tested for HRHPV, 27.2% (n = 239) were ≤ 40 years. In this age group HRHPV was detected in 33.5% (n = 80) of women, and 23.8% (n = 19) were women < 30 years. Out of 239 women tested for HRHPV, 60.2% had an abnormal Pap smear result. Therefore, 40.7% (n = 59) of HRHPV-positive women had an abnormal Pap test result. Women with a normal Pap test result had an HRHPV-positive test in 22.3% (n = 21) of cases. The results obtained contribute to the knowledge about HPV prevalence and the incidence of squamous cell abnormalities in the most populous canton in Bosnia and Herzegovina, possibly reflecting the situation nationally. The high prevalence of HRHPV in women of reproductive age calls for urgent implementation of an organized cervical cancer screening program and HPV vaccination.

Non-Adherence To Childhood HPV Vaccination Is Associated With Non-Participation In Cervical Cancer Screening - A Nationwide Danish Register-Based Cohort Study.

BackgroundThe combination of organized cervical cancer screening and childhood HPV vaccination programs has the potential to eliminate cervical cancer in the future. However, only women participating in both programs gain the full protection, and combined non-attenders remain at high risk of developing cervical cancer. Our aim was to analyze the association between non-adherence to HPV vaccination and non-participation in cervical cancer screening for the total population and stratified by native background and parental education.ParticipantsWomen born in 1993 eligible for both childhood HPV vaccination and first cervical cancer screening.AnalysisLogistic regression models were used to estimate the odds ratio (OR) of non-participation in cervical cancer screening with 95% confidence intervals (CI). Stratified and adjusted logistic regression models were used along with the Wald test in order to test for interaction.Results24,828 women were included in the study. Among vaccinated women, 61.4% participated in cervical cancer screening; only 39.0% of unvaccinated women participated in cervical cancer screening. Unvaccinated and unscreened women were often non-native and had the lowest socio-economic status, whereas vaccinated and screened women were often native and had the highest socio-economic status. The adjusted OR for non-participation in cervical cancer screening was 2.07 [95% CI: 1.88–2.28] for unvaccinated compared to vaccinated women. After stratifying by country of origin, unvaccinated natives had the highest adjusted OR of not participating in cervical cancer screening compared to non-native women from both western and non-western countries (adjusted ORs of 2.2 [95% CI: 2.0–2.4], 1.3 [95% CI: 0.6–2.8], and 1.5 [95% CI: 1.1–2.0], respectively) (Wald test p=0.019).ConclusionAmong natives, non-adherence to HPV vaccination and non-participation in screening seem to be signs of generally poor health-preventive behavior, whereas among non-natives from non-western countries, non-attendance in HPV vaccination and cervical cancer screening seem to be influenced by unrelated factors. Therefore, a differentiated and culturally sensitive approach is needed to enhance overall cervical cancer preventive behavior across different nativities.

Use of Appropriate Technology to Improve Cervical Cancer Prevention and Early Detection: Experience in Jos, Nigeria

PURPOSE In absolute numbers, Nigeria is one of the countries with the highest burden and mortality as a result of invasive cervical cancer (ICC), with more than 53 million women at risk. The coverage for available cervical cancer screening by conventional cytology is less than 9% of the population. Also, the lack of a national human papillomavirus vaccination program and organized cervical cancer screening services could partly be responsible for the more than 14,000 new ICC cases and 8,000 deaths attributable to ICC in Nigeria every year. Furthermore, the prevailing challenges of diagnosis at advanced stages in more than 80% of ICC cases with a paucity of trained oncologists and poor treatment infrastructures often result in high death rates. These problems make the use of appropriate technology to improve screening, early detection, and treatment of precancerous conditions a novel strategy for achieving quality cancer care in our setting. The objective of this study was to discuss our experience with use of available and resource-appropriate technology to improve cervical cancer care and outcomes in Jos, Nigeria. METHODS A critical review of cervical cancer prevention, diagnosis, and treatment facilities and outcomes in Nigeria was done. This background information provided justification for the use of resource-appropriate technology for improving quality of cervical cancer prevention and treatment outcomes in resource-limited settings. We also gleaned from specific experiences of cervical cancer screening, follow-up, and treatment of both precancer and early invasive cervical cancer in Jos, Nigeria. RESULTS The main factors responsible for increasing burden and poor cervical cancer outcomes in Nigeria and other resource-limited settings in sub-Saharan Africa include: HIV infection; lack of organized cervical cancer screening programs, with poor coverage even when opportunistic screening is available; weak health care system; illiteracy; and poor human papillomavirus vaccination coverage. Some of the major challenges in treatment of cervical cancer include: late presentation, with poor treatment infrastructures; paucity of trained gynecologic oncologists, medical oncologists, and other disciplines needed to improve quality of cancer care; and poor access to available prevention and treatment services, with limited/no health insurance coverage. CONCLUSION Resource-limited settings should leverage the widespread availability of mobile phones to improve cervical cancer education and scheduling for screening, follow-up, and treatment of precancerous conditions. Also, the use of radio talks can reach women in remote locations. Adoption and use of novel testing technology, such as self-sample collection for human papillomavirus DNA testing, is also advocated. Our team in Jos, with collaboration with Northwestern University, is also looking ahead through molecular research on how epigenetic and microbiome biomarkers could improve prevention and early detection of precancer and ICC as a strategy for improving outcomes in our population. Also, the utility of low-cost treatment modalities, such as battery-operated thermocoagulation, could improve coverage for treatment of cervical precancer. Finally, resource-limited settings should train general gynecologists with interest in oncology to acquire specific competencies for locoregional surgical control, particularly for early-stage cervical cancer. Given the identified challenges, the judicious use of these resource-appropriate technologies may improve quality of cancer care and outcomes in resource-limited settings.

Exploratory analysis of barriers and facilitators to cervical cancer care in rural Tamil Nadu, India.

125 Background: Approximately 20% of cervical cancer deaths worldwide occur in India, most notably in rural areas. The key to addressing the cervical cancer epidemic is early detection and treatment of precancerous cervical lesions. Many studies that assess barriers to cervical cancer care in India focus on individual level factors, such as awareness and education. Given the disparities in cervical cancer in India, particularly between rural and urban settings, a comprehensive, multi-level approach to evaluating barriers and facilitators to care is needed. Methods: In December 2018, we used semi-structured interviews and direct observation of 15 community health workers, medical officers and gynecologic oncologists to explore the multi-level barriers and facilitators to cervical cancer care in rural Tamil Nadu. Data collection occurred within an existing organized cervical cancer screening program and was guided by the social-ecological model. Results: Barriers and facilitators to cervical cancer screening and treatment of precancerous lesions were identified at all levels of the social-ecological model. Barriers included fear of and travel distance to urban centers for treatment (individual), limited social support (interpersonal), lack of rural clinical facilities that provide treatment (organizational), competing community health initiatives (community), and lack of cohesive national screening and treatment guidelines (policy). Facilitators included travel distance to local screening services (individual), access to community health workers (interpersonal), institutional initiatives to increase screening access (organizational), mass awareness campaigns (community), and Tamil Nadu State priorities to improve cervical cancer care (policy). Conclusions: This assessment underscores the gap between cervical cancer screening and treatment in rural Tamil Nadu. This data will inform the development of a multi-faceted intervention, targeting all levels of the social-ecological model, to improve the linkage between cervical cancer screening and treatment for precancerous cervical lesions to decrease the burden of disease and mortality in India.

HIGH-RISK HPV testing as the primary screening method in an organized regional screening program for cervical cancer: the value of HPV16 and HPV18 genotyping?

Since 2012, testing high-risk (HR)HPV has been used as the primary screening test for women ≥35years attending the organized cervical cancer screening program in the city of Tampere. We evaluated the contribution of HPV16/18 genotyping. Data from 2012 and 2013, and the follow-up samples in 2013 and 2014, respectively, were analyzed. Abbott RealTime High-Risk HPV test detecting 14 HRHPV genotypes combined with concurrent genotyping for HPV16 and HPV18 was used. HPV was positive in 794 samples out of 11346 HPV tested women (7%). HPV16/18 was represented in 22% of HPV-positive cases. Negative cervical cytology (NILM) was reported in 51% of HPV-positive samples. HPV16/18 genotype was accompanied with 50% of HSIL/ASC-H cases. The predominance of HPV16/18 in higher grade lesions was even more evident in cervical biopsies as 57% of CIN3 cases were associated with HPV16/18, and only 20% of carcinomas were associated with nonspecified high-risk (NSHR) genotypes. In agreement with previous studies HPV16/18 genotypes caused higher grade cytological and histological changes/pathologies than NSHR genotypes in primary screening. Nevertheless, the majority of HRHPV genotypes detected in the screened population were nonHPV16/18, and especially within persistent infections, precancerous lesions were found also among women with NSHR genotypes.

High-Grade Cervical Intraepithelial Neoplasia in Human Papillomavirus Self-sampling of Screening Non-attenders

(Abstracted from Br J Cancer 2018;118:138–144) Denmark has an organized cervical cancer screening program; every 3 years, women aged 23 to 49 years are invited for screening, and every 5 years, women 50 to 65 years of age are invited. The large proportion of invited women who are not screened (nonattenders) is a major challenge in preventing cervical cancer.

PP62 Cost-Effectiveness Of Cervical Cancer Screening In Estonia

IntroductionIn Estonia, organized cervical cancer screening program is targeted at women aged 30–55(59) years and Pap-tests are taken every five years. Since cervical cancer is associated with human papillomavirus (HPV), a number of countries have introduced the HPV-test as the primary method of screening. The objective of this study was to evaluate the cost-effectiveness of organized cervical cancer screening program in Estonia by comparing HPV- and Pap-test based strategies.MethodsFor the cost-effectiveness analysis, a Markov cohort model was developed. The model was used to estimate costs and quality-adjusted life-years (QALYs) of eight screening strategies, varying the primary screening test and triage scenarios, upper age limit of screening, and testing interval. Incremental cost-effectiveness ratios (ICERs) were calculated in comparison to current screening practice as well as to the next best option. Sensitivity analysis was performed by varying one or more similar parameter(s) at a time, while holding others at their base case value. The analysis was performed from the healthcare payer perspective adopting a five percent annual discount rate for both costs and utilities.ResultsIn the base-case scenario, ICER for HPV-test based strategies in comparison to the current screening practice was estimated at EUR 8,596–9,786 per QALY. For alternative Pap-test based strategies ICER was estimated at EUR 2,332–2,425 per QALY. In comparison to the next best option, HPV-test based strategies were dominated by Pap-test based strategies. At the cost-effectiveness threshold of EUR 10,000 per QALY Pap-testing every three years would be the cost-effective strategy for women participating in the screening program from age 30 to 63 (ICER being EUR 3,112 per QALY).ConclusionsDecreasing Pap-test based screening interval or changing to HPV-test based screening can both improve the effectiveness of cervical cancer screening program in Estonia, but based on the current cost-effectiveness study Pap-test based screening every three years should be preferred.

Cervical morbidity in Alsace, France: results from a regional organized cervical cancer screening program.

In 1994, a pilot program of cervical cancer screening was introduced in the Alsace region, France. Women aged 25-65 years were proposed to have one Pap smear every 3 years. The objective was to assess cervical morbidity in Alsace before the human papillomavirus vaccinated population reaches the age of screening. Data on cervical lesions and cancers were collected by EVE for the period September 2008 to August 2011 from existing medical services and cytopathology laboratories in Alsace. Cytological and histological data were completed with data from the two cancer registries covering the region (Bas-Rhin and Haut-Rhin). Cancer incidence rates were computed for the target population (truncated to 25-64 years) and were age standardized according to the world reference population. World standardized incidence rates for the whole female population were obtained from the two cancer registries. During 2008-2011, 565 153 smears were performed in 498 913 women aged 25-64 years, representing an average of 1.13 smears/woman and 1.62 smears/screened woman. The overall screening coverage was 70.1% over the 3-year period. Histologically confirmed high-grade lesions were found in 2303 women (0.5%). Moreover, 215 cervical cancers were reported among women aged 25-64 years (crude and standardized truncated incidence rate of 10.6 and 10.0/100 000 women-years, respectively). The overall screening coverage of 70% at 3 years is higher than the national rate (57%), and the overall cancer incidence of 5.5/100 000 is below the national French level. The EVE database will be useful to assess trends in cervical morbidity over time and to further assess the effect of screening as well as of human papillomavirus vaccination.

Challenges of Planning a Sustainable Comprehensive Cervical Cancer Prevention Program in Low-Resource Settings

Background and context: Advancement in science and technology has been appropriately applied in the prevention of cervical cancer that it is not unreasonable to conclude that cervical cancer is potentially an eradicable disease. While there is significant reduction in both incidence and mortality from cervical cancer in developed countries that have instituted organized cervical cancer prevention programs, the incidence and mortality from cervical cancer in developing countries are either static or on the rise. This has been reported to be largely due to lack of organized cervical cancer screening program in developing countries despite the availability of effective screening methods appropriate for low resource settings. The challenges of planning a sustainable comprehensive cervical cancer control program in low resource settings are hereby highlighted based on experience from execution of Global Scholar's seed grant of American Cancer Society. Aim: To document innovative approach to overcoming challenges of planning a comprehensive cervical cancer care and control in low resource settings. Strategy/Tactics: The strategy recommended by Alliance for Cervical Cancer Prevention in Planning and Implementing Cervical Cancer Control Program: A guide for manager was adopted in planning of a comprehensive cervical cancer prevention program for Kebbi state. Program/Policy process: Learning from HIV program implementation, the program adopted policy of integration into existing health structure rather than creating a vertical program. Conscious effort was being made at every stage not to create impression of a special intervention program deserving extra pay for the healthcare professionals nor incentives other than good health for the clients. Outcomes: A local guideline was developed based on a trade-off consideration of evidence of efficacy, cost-effectiveness and sustainability within the context of prevailing local challenges. What was learned: Literature on cervical cancer prevention seems to be skewed in favor of search for appropriate screening method for low resource settings rather than programmability of cervical cancer prevention and control strategies. No individual component of cervical cancer prevention will impact on the burden of cervical cancer independent of the other components. For a cervical cancer program to be impactful, all the components; awareness creation, acceptable screening method, treatment and follow-up of screen positive women, call and recall of clients, treatment of invasive lesions must not only all be available (albeit at different levels of sophistications) but must also be linked. Rapidly evolving science ironically could pose a significant challenge to sustainable execution of a comprehensive cervical cancer prevention program in low resource settings if there is no guideline to guide interfacing of program with evolving science.

Pre-vaccination prevalence of high-risk human papillomaviruses (HPV) in women from Kosovo and their related sociodemographic characteristics

Kosovo's current health care system does not support organized nationwide cervical cancer screening and human papillomavirus (HPV) vaccination programs. To date, no reliable data are available on cervical cancer incidence and mortality in Kosovo, or on high-risk HPV (HR-HPV) prevalence and HPV type distribution. Our aim is to determinate the pre-vaccination prevalence and distribution of HR-HPVs and to assesses the associations between sociodemographic characteristics and increased risk of HPV infection in women from Kosovo. Detection of HR-HPV DNA in cytologically evaluated cervical smears was performed using a clinically validated Abbott RealTime High Risk HPV test, Roche Linear Array HPV Genotyping Test, HPV52 type-specific real-time PCR and an in-house GP5+/GP6+/68 PCR. The crude overall prevalence of any of the HR-HPVs was estimated at 13.1% (26/199; 95% confidence interval (CI): 9.1-18.5%), with HPV16 being the most common type (7/26, 26.9%), followed by HPV31 and HPV51, each detected in 4/26 (15.4%) cervical specimens, HPV18, detected in 3/26 (11.5%) specimens, HPV52 and HPV66, each detected in 2/26 (7.7%) specimens, and HPV33, HPV45, HPV56, and HPV58, each detected in a single (3.9%) specimen. Women over 40 (OR = 0.36), older than 18 at sexual debut (odds ratio (OR) = 0.28), those that had delivered at least one child (OR = 0.32), and those that had a history of pregnancy termination (OR = 0.39) were at lower risk for HPV infection. Because more than 70% of cervical precancerous lesions could have been prevented in Kosovo using nationwide HPV-based cervical cancer screening and HPV vaccination, it is of outmost importance to implement both programs in the national health care system as soon as possible.

Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months

There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations. To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control). Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible. A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing. The primary outcome was the cumulative incidence of CIN3+ 48 months following randomization. The cumulative incidence of CIN2+ was a secondary outcome. Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). The CIN2+ incidence rate at 48 months was 5.0/1000 (95% CI, 3.8-6.7) in the intervention group and 10.6/1000 (95% CI, 8.7-12.9) in the control group. The CIN2+ risk ratio was 0.47 (95% CI, 0.34-0.67). Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 [95% CI, 0.8-2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13-0.48]). Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness. isrctn.org Identifier: ISRCTN79347302.

Knowledge, attitudes, and practices toward cervical cancer prevention among women in Kampong Speu Province, Cambodia

BackgroundThere is little information concerning the preventive behaviors against cervical cancer among women in Cambodia, a country without organized cervical cancer screening programs and national human papillomavirus (HPV) vaccination policies. We aimed to examine the cervical cancer knowledge, attitudes, and practices as well as cervical cancer prevention methods among Cambodian women.MethodsA community-based cross-sectional survey on cervical cancer prevention was conducted. We conducted a face-to-face interview survey for women aged 20–69 years who lived in Kampong Speu Province. The data collection was conducted by a nurse and a trained health worker using a structured questionnaire from January 8 to February 19, 2016. The questionnaire comprised 46 questions on demographic and reproductive characteristics, knowledge of cervical cancer, related risk factors and preventive methods, and attitudes toward and practices of Pap test and HPV vaccination. A logistic regression analysis was used to evaluate the relationship between preventive behaviors against cervical cancer and related factors such as age, education, income, and knowledge of cervical cancer.ResultsAmong the 440 respondents, 74 and 34% of women had heard about cervical cancer and the Papanicolaou (Pap) Smear test, respectively, and 7% of women had ever been screened by a Pap test. The participants showed high willingness to undergo a Pap test (74%). Furthermore, 35% of women were aware that cervical cancer is preventable by vaccination and 62% of women were willing to get the HPV vaccine, but only 1% of women had been vaccinated against HPV. Women of a younger age (odds ratio: 76.7; 95% confidence interval: 19.2–306.5 among women aged 20–29 years compared to 60–69 years, P-for-trend< 0.0001) and those who were married (odds ratio: 2.8; 95% confidence interval: 1.3–6.3) were more likely to be willing to receive the vaccination.ConclusionsWomen in the Kampong Speu province of Cambodia had a low awareness of cervical cancer screening and rarely practiced cervical cancer screening. However, the willingness to get Pap test and HPV vaccination is high.

Seroprevalences of Antibodies to 11 Human Papillomavirus (HPV) Types Mark Cumulative HPV Exposure

The antibody responses against human papillomavirus type 16 (HPV-16) and HPV-18 are well known, but many genital HPV types are oncogenic. We assessed the correlation between detection of type-specific HPV DNA and antibodies for 11 HPV types. A total of 2024 women attending the organized national cervical cancer screening program in Slovenia were tested for cervical high-risk HPV DNA (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, -59, and -68) and serum anti-HPV antibodies. Of these, 1848 women were tested with the same methods 3 years earlier. Type-specific antibodies against 10 of 11 HPV types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, and -58) were associated with concomitant presence of type-specific DNA (median odds ratio [OR], 7.5; 95% confidence interval [CI], 2.2-26.1). When the concomitant presence of type-specific HPV DNA at the 3-year visit was combined with the presence of the same HPV DNA type 3 years earlier, the statistical precision was greatly improved, and antibodies against all 11 types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, and -59) were associated with the presence of DNA of the same HPV type (median OR, 7.4; 95% CI, 4.2-12.8). Sensitivity had a slight tendency to increase (from 47% to 52%) when DNA positivity at the earlier time point was included, whereas specificity was the same (88%). Seroconversion was associated with previous HPV DNA positivity. Seropositivity mostly remained stable during the observation period. For 11 HPV types, type-specific seropositivity was associated with the presence of DNA of the same HPV type (either concomitantly or previously). Antibodies to these HPV types mark cumulative HPV exposure.

Cervical Cancer, Human Papillomavirus Infection, and Vaccine-Related Knowledge: Awareness in Chinese Women.

Cervical cancer (CC) has a high incidence and mortality and is accompanied by lack of organized CC screening programs, lack of health-care facilities, and a lack of human papillomavirus (HPV) vaccination among female population in the world, particularly China. We recruited 487 females who visited the outpatient department of the First People’s Hospital of Yunnan Province from November 2015 to January 2016 to complete a standardized-designed questionnaire. We found that only 39.6% of the females knew about the role of HPVs in the development of cervical cancer. Moreover, none of the females knew that HPV could cause penile carcinomas, perianal carcinomas, and head and neck carcinomas. The majority of the participants acquired information about cervical cancer, HPV, and the HPV vaccine from medical workers. Only 15.6% of the recruited females had heard about the HPV vaccine. The overall HPV vaccine acceptance rate was higher (91.2%) if the vaccine was available free of cost. In this study, we found high acceptability of the HPV vaccine in Chinese women and high awareness about cervical cancer. However, very low levels of knowledge about HPVs and their role in cancer development among the recruited women is alarming. Therefore, it is very important to initiate educational programs to raise awareness and knowledge about cervical cancer, HPV, and the HPV vaccine in this region.

Effect of naturally acquired type-specific serum antibodies against human papillomavirus type 16 infection

BackgroundWhile vaccine-induced antibodies are known to confer protection against incident human papillomavirus (HPV) infection, there is inconsistent data regarding the protective effect of naturally acquired anti-HPV antibodies. ObjectivesTo estimate the protective effect of naturally acquired anti-HPV16 serum antibodies against incident anogenital infection with HPV16 in females aged 20–64 years and to assess whether antibodies influence the persistence/clearance of anogenital HPV16 infection. Study design4432 women attending the organized national cervical cancer screening program in Slovenia were initially enrolled. 2199 and 1848 women had valid HPV DNA results obtained using PCR-based assays and HPV antibody serotyping results obtained using pseudovirion-based serological assay, at baseline and at three-year follow-up, respectively. ResultsBaseline HPV16 seroprevalence was 2.4-fold higher among HPV16 DNA-positive women (55.7% vs. 23.2%; p<0.01). Baseline HPV16 DNA-positive/seronegative women frequently acquired anti-HPV16 antibodies during follow-up (OR=8.2; 95% CI: 3.8–17.8). Baseline anti-HPV16 antibodies persisted at follow-up, irrespective of baseline HPV16 DNA status (OR=40.6; 95% CI: 30.3–54.5). Baseline HPV16 DNA-negative/seropositive women were less likely to acquire HPV16 infection at follow-up (unadjusted OR=0.2; 0.1–0.9). However, the age-adjusted association was non-significant (adjusted OR=0.3; 0.1–1.2). The tendency for protective effect was stronger among women older than 25 years (OR=0.2; 0.03–1.8). Baseline anti-HPV16 antibodies were not associated with persistence/clearance of HPV16 infection at follow-up (OR=0.8; 0.3–1.9). ConclusionsNaturally acquired anti-HPV16 serum antibodies appeared to protect against anogenital HPV16 infection, but this association was at least partially confounded by age. Baseline anti-HPV16 serum antibodies did not influence persistence/clearance of HPV16 infection at follow-up.

Assessment of the pilot program for cervical cancer screening by health visitors

Within the tender (6.1.3.A-13/1-2013-0001) supported by the European Union, we wished to involve health visitors into the organized cervical cancer screening program. The aim of our survey was to assess the satisfaction of health visitors, instructors, and that of the teaching aids. Furthermore, we wished to assess whether the teaching materials met the expectations. Satisfaction of the health visitors was assessed by a survey, in four groups of questions. These involved the assessment of the instructors, the teaching aids, evaluation of the further training day, and the compliance with the knowledge of training. Period for completion of the questionnaires lasted from October to December in 2014. We used descriptive statistics for data evaluation. Data of 2148 health visitors was evaluated. They rated the performance of gynecologist-obstetricians 4.65, that of health visitors 4.61, that of public health professionals 4.56, and that of IT specialists 4.52. 98% of the teaching aids were useful for them and the acquired knowledge was appropriate with their expectations. The health visitors were satisfied with the theoretical instruction within the pilot program. The professionally well prepared health visitors may contribute to the success of the cervical cancer screening program. Orv. Hetil, 2017, 158(12), 461-467.

Cost-effectiveness of increasing cervical cancer screening coverage in the Middle East: An example from Lebanon

BackgroundMost cervical cancer (CC) cases in Lebanon are detected at later stages and associated with high mortality. There is no national organized CC screening program so screening is opportunistic and limited to women who can pay out-of-pocket. Therefore, a small percentage of women receive repeated screenings while most are under-or never screened. We evaluated the cost-effectiveness of increasing screening coverage and extending intervals. MethodsWe used an individual-based Monte Carlo model simulating HPV and CC natural history and screening. We calibrated the model to epidemiological data from Lebanon, including CC incidence and HPV type distribution. We evaluated cytology and HPV DNA screening for women aged 25–65years, varying coverage from 20 to 70% and frequency from 1 to 5years. ResultsAt 20% coverage, annual cytologic screening reduced lifetime CC risk by 14% and had an incremental cost-effectiveness ratio of I$80,670/year of life saved (YLS), far exceeding Lebanon’s gross domestic product (GDP) per capita (I$17,460), a commonly cited cost-effectiveness threshold. By comparison, increasing cytologic screening coverage to 50% and extending screening intervals to 3 and 5years provided greater CC reduction (26.1% and 21.4, respectively) at lower costs compared to 20% coverage with annual screening. Screening every 5years with HPV DNA testing at 50% coverage provided greater CC reductions than cytology at the same frequency (23.4%) and was cost-effective assuming a cost of I$18 per HPV test administered (I$12,210/YLS); HPV DNA testing every 4years at 50% coverage was also cost-effective at the same cost per test (I$16,340). Increasing coverage of annual cytology was not found to be cost-effective. ConclusionCurrent practice of repeated cytology in a small percentage of women is inefficient. Increasing coverage to 50% with extended screening intervals provides greater health benefits at a reasonable cost and can more equitably distribute health gains. Novel HPV DNA strategies offer greater CC reductions and may be more cost-effective than cytology.

Study protocol of the CHOiCE trial: a three-armed, randomized, controlled trial of home-based HPV self-sampling for non-participants in an organized cervical cancer screening program.

BackgroundThe effectiveness of cervical cancer screening programs is challenged by suboptimal participation and coverage. Offering cervico-vaginal self-sampling for human papillomavirus testing (HPV self-sampling) to non-participants can increase screening participation. However, the effect varies substantially among studies, especially depending on the approach used to offer HPV self-sampling. The present trial evaluates the effect on participation in an organized screening program of a HPV self-sampling kit mailed directly to the home of the woman or mailed to the woman’s home on demand only, compared with the standard second reminder for regular screening.Methods/designThe CHOiCE trial is a parallel, randomized, controlled, open-label trial. It will include 9327 women aged 30–64 years who are living in the Central Denmark Region and who have not participated in cervical cancer screening after an invitation and one reminder. The women will be equally randomized into three arms: 1) Directly mailed a second reminder including a HPV self-sampling kit; 2) Mailed a second reminder offering a HPV self-sampling kit, to be ordered by e-mail, text message, phone, or through a webpage; and 3) Mailed a second reminder for a practitioner-collected sample (control group). The primary outcome will be the proportion of women in the intervention groups who participate by returning their HPV self-sampling kit or have a practitioner-collected sample compared with the proportion of women who have a practitioner-collected sample in the control group at 90 and 180 days after mail out of the second reminders. Per-protocol and intention-to-treat analyses will be performed. The secondary outcome will be the proportion of women with a positive HPV self-collected sample who attend follow-up testing at 30, 60, or 90 days after mail out of the results.DiscussionThe CHOiCE trial will provide strong and important evidence allowing us to determine if and how HPV self-sampling can be used to increase participation in cervical cancer screening. This trial therefore has the potential to improve prevention and reduce the number of deaths caused by cervical cancer.Trial registrationCurrent Controlled Trials NCT02680262. Registered 10 February 2016.

Disengagement of general practitioners in cervical cancer screening.

In the absence of organized cervical cancer screening (CCS) programs, gynecologists remain principal actors in obtaining a Pap smear, followed by general practitioners (GPs). In France, with the growing scarcity of gynecologists and social inequalities in access to opportunistic screening, GPs are valuable resources for women's gynecologic follow-up. We aimed to investigate the characteristics of GPs who do not perform CCS, analyzing the effect of GPs' sex and their evolution over time. On the basis of data from three cross-sectional surveys conducted among representative samples of French GPs in 1998, 2002, and 2009 (n=5199), we constructed univariate and multivariate logistic mixed models (level 2: county, level 1: GP) with random intercept stratified on GPs' sex to investigate the characteristics of the GPs associated with no practice of CCS ever. Almost one-third of all GPs did not perform CCS ever and it increased with time. Male GPs were always more likely not to perform it (odds ratio=0.50, 95% confidence interval=0.42-0.59). The percentage of GPs not performing CCS increased more markedly among male than among female GPs, and increased more among the youngest age group. Increasingly fewer GPs engage in CCS when the growing scarcity of medical gynecologists calls for more participation. Female GPs remain significantly more active in CCS than male GPs. The participation in CCS is determined differently according to the practitioner's sex.

Abnormal cervical cytology and health care use: A population-based register study

ObjectiveThis study aimed to assess the long-term use of health care services in women with abnormal cytology results compared to women with normal cytology results. MethodsWe did a nationwide population-based study, using women aged 23 to 59years participating in the national organized cervical cancer screening program. We included a study population of 40,153 women with abnormal cytology (exposed) and 752,627 women with normal cytology (non-exposed). We retrieved data from the Danish Civil Registration System, the Danish Pathology Data Bank, the National Health Service, the National Patient and the National Prescription Register. We calculated the frequencies of contacts to general practitioner (GP), to private psychiatrist and/or psychologist, admissions to hospitals and use of prescription drugs. These frequencies were calculated separately in the 5-year period “before” the cytology result and for the 5-year period “after” the result. ResultsDuring the “before” period exposed women had more contacts to GPs, more contacts to psychologists/psychiatrist, and more hospital admissions than non-exposed women. In both exposed and non-exposed women, health care use increased from the “before” to the “after” period. This increase was significantly higher for exposed than non-exposed women regarding contacts to GP, admissions to hospitals, and drug use. ConclusionWomen with abnormal cytology results constitute a selected group with a higher health care use than other women even before they have the abnormal cytology. This difference is further enhanced after the abnormal cytology result.