Management of low‐grade cervical abnormalities detected at screening: which method do women prefer?

Objective:  To establish whether women with low-grade abnormalities detected during screening for cervical cancer prefer to be managed by cytological surveillance or by immediate colposcopy.
Methods:  TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal smears) is a randomized controlled trial comparing alternative management strategies following the screen-detection of low-grade cytological abnormalities. At exit, a sample of TOMBOLA women completed a questionnaire eliciting opinions on their management, contingent valuations (CV) of the management methods and preferences. Within-trial quality of life (EQ-5D) data collected for a sample of TOMBOLA women throughout their follow-up enabled the comparison of self-reported health at various time points, by management method.
Results:  Once management had been initiated, self-reported health in the colposcopy arm rose relative to that in the surveillance arm, although the effect was short-term only. For the majority of women, the satisfaction ratings and the CV indicated approval of the management method to which they had been randomized. Of the minority manifesting a preference for the method which they had not experienced, relatively more would have preferred colposcopy than would have preferred surveillance.
Conclusions:  The findings must be interpreted in the light of sample bias with respect to preferences, whereby enthusiasm for colposcopy was probably over-represented amongst trial participants. The study suggests that neither of the management methods is preferred unequivocally; rather, individual women have individual preferences, although many would be indifferent between methods.     

High prevalence of cervical squamous intraepithelial lesions in women on antiretroviral therapy in Cameroon: Is targeted screening feasible?

Background: Cervical cancer is the most common cancer in women in low-income countries. Although cervical cancer incidence and mortality is higher in HIV-positive women, resource limitations restrict the implementation of systematic screening programs in these women. We explored the potential for targeted screening by assessing the prevalence, severity and predictors of cervical squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon. Methods and findings: We conducted a cross-sectional study of women on antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical information was obtained from eligible women. Cervical exfoliated cells were then collected, a conventional cytology performed and epithelial lesions classified according to the Bethesda 2001 system. A total of 282 women, aged 19–68 years, were enrolled in this study. The median CD4 count was 179 cells/microliter (interquartile range: 100–271). SILs were detected in 43.5% of the 276 women with satisfactory samples: including atypical squamous cells of unknown significance (ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the demographic or clinical characteristics considered significantly predicted the presence of any SILs or the presence of severe lesions requiring colposcopy. Conclusion: The prevalence of SIL in women on antiretroviral therapy in Cameroon was high underscoring the need for screening and care in this population. In the absence of any accurate demographic or clinical predictor of SIL, targeted screening does not seem feasible. Alternative affordable screening options need to be explored.     

Trends in socioeconomic inequalities in cervical,breast, and colorectal cancer screening participation among women in Japan, 2010–2019

BackgroundIt is known that socioeconomic status (SES) influences the outcome of cancer treatment and this could partly be explained by decreased use of cancer screening services by people of lower SES. Many studies have indicated that low SES, including low educational attainment or unstable employment, was related to nonparticipation in cancer screening. However, studies investigating trends in SES inequalities within cancer screening participation are limited. Our objective was to examine trends in SES inequalities in cervical, breast, and colorectal cancer screening participation among women in Japan between 2010 and 2019.MethodsWe analyzed 189,442, 168,571, 163,341, and 150,828 women in 2010, 2013, 2016, and 2019 respectively, using nationally representative cross-sectional surveys. The main outcome variables are participation in each cancer screening. We used educational attainment and employment status as measures for SES. Multivariable logistic regression analysis, adjusted for age, marital status, educational attainment, and employment status was performed to evaluate the associations between SES and nonparticipation in each cancer screening.ResultsOverall participation rates in each cancer screening increased between 2010 and 2019. Low educational attainment and non-permanent employment status were related to nonparticipation in each cancer screening and inequality according to employment status increased within each screening participation during the study period. For example, dispatched workers were more likely to not participate in cervical cancer screening than permanent workers: in 2010, [aOR 1.11 95 %CI: 1.01 –1.21], and in 2019, [aOR 1.46 95 %CI: 1.34–1.60]. The inequality was greatest in colorectal cancer screening nonparticipation, followed by breast and cervical screening.ConclusionsAlthough the participation rates in each cancer screening have increased, inequality in participation in terms of employment status widened among women in Japan between 2010 and 2019. Reducing inequalities in cancer screening participation is essential for cancer screening intervention policies.     

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia,Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.     

Costs and benefits of cervical screening. II. Is it worthwhile reducing the screening interval from 5 to 3 years?

A reduction in screening interval from 5 years to 3 years would greatly increase the cost of the programme, but would save few extra lives. The cost per life saved would be around £250 000 at 1995 prices, or around £8000 per life per year saved. There would in addition be human costs for the women screened. The opportunity cost of reducing the interval may be too great, since it is likely that the Health Service would achieve greater health benefits by investing the funds in other health care activities.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility

Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.     

Liquid‐based cytology: is this the way forward for cervical screening?

Liquid-based cytology (LBC) is currently being marketed as an alternative methodology to replace the conventional PAP smear in cervical cytology. A substantial body of literature exists in support of LBC, some of which is at least partially sponsored by product manufacturers. The majority of published literature in support of LBC employs Bethesda reporting terminology. In this study we have analysed published raw data and presented this in NHSCSP terminology. Claims relating to sensitivity, specificity and smear adequacy have then been considered with reference to this data. Our analysis of existing data does not support the nationwide implementation of LBC at present. Further studies are recommended in order to evaluate the place of this technology within the NHSCSP.     

The advantages of incorporating liquid-based cytology (TACAS™) in mass screening for cervical cancer

We incorporated liquid-based cytology (LBC) in population-based screening for cervical cancer. The usefulness of using LBC in mass screening for cervical cancer was examined. From 2009 to 2014, 157,061 individuals underwent mass screening for cervical cancer in Aomori Prefecture. From 2009 to 2011, cells were collected from 82,218 individuals and the specimens were conventionally prepared (CP). From 2012 to 2014, cells were collected from 74,843 individuals and the specimens were prepared using LBC (TACAS?). Cytology results for the 2 sets of specimens were compared and differences in cytologic features were examined. ASC-US and more severe lesions were detected at a rate of 1.13 % by CP and 1.44 % by LBC, so LBC had a 1.3-fold higher rate of detection. LBC had a 1.6-fold higher rate of LSIL detection and a 1.2-fold higher rate of HSIL detection. CP detected cancer in 20 cases at a rate of 0.024 % while LBC detected cancer in 18 cases at a rate of 0.024 %. Cytodiagnosis of the 18 cases of SCC that LBC identified revealed that 7 were SCC, 8 were HSIL, and 3 were ASC-H. Atypical cells tended to be smaller with TACAS?. LBC reduced the time needed for microscopic examination of a single specimen by 42 % in comparison to CP. LBC using TACAS? allowed the detection of slight lesions and slight changes in cells. LBC can lessen the burden on medical personnel and may lead to improved accuracy.     

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

Background: To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. Methods: This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test. Results: Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%). Conclusions: Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.     

European trends in cervical cancer mortality in relation to national screening programs, 1985–2014

BackgroundCervical cancer is the fourth leading oncological cause of death in women. Variable trends in cervical cancer mortality have been observed across Europe, despite the widespread adoption of screening programs. This variability has previously been attributed to heterogeneity in the quality of screening programs.MethodsAge-standardized cervical cancer death rates for European countries between 1985 and 2014 were analyzed using Joinpoint regression. Countries were dichotomized based on year of implementation and population invitational coverage of national population-based cervical cancer screening programs. National cervical cancer mortality trends during the study period were compared based on this classification.ResultsDecreasing trends in mortality were observed in all European countries with the specific exceptions of Bulgaria, Greece and Latvia. The highest rates of cervical cancer mortality throughout the study period were in Romania (16.0-14.9/100,000) and the lowest rates in Italy (1.4-1.2/100,000). The greatest percentage decline in mortality was observed in the United Kingdom and the greatest absolute reduction in mortality was seen in Hungary. European countries which implemented a national population-based cervical cancer screening program prior to 2009 demonstrated greater improvements in cervical cancer mortality outcomes compared to those that did not (p = 0.016).ConclusionCervical cancer mortality is improving in most European countries; however, substantial variation remains. Trends in mortality were associated with the time of implementation of national population-based cervical screening programs.     

Recruitment of young women to a trial of chlamydia screening – as easy as it sounds?

Background

In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons.

Methods/Design

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.     

Which women default from follow‐up cervical cytology tests? A cohort study within the TOMBOLA trial

L. Sharp, S. Cotton, A. Thornton, N. Gray, D. Whynes, L. Smart, N. Waugh, I. Duncan, M. Cruickshank and J. Little, on behalf of the TOMBOLA Group Which women default from follow‐up cervical cytology tests? A cohort study within the TOMBOLA trial Objective: To identify factors associated with default from follow‐up cervical cytology tests. Methods: A cohort study was conducted involving 2166 women, aged 20–59, with recent low‐grade cervical cytology taken within the NHS Cervical Screening Programmes in Scotland and England, and managed by 6‐monthly cytology in primary care. For the first (6‐month) and second (12‐month) surveillance cytology tests separately, women were categorized as ‘on‐time attendees’ (attended ≤6 months of test being due), ‘late attendees’ (attended greater than 6 months after test was due) or ‘non‐attendees’ (failed to attend). Multivariate odds ratios (ORs) were computed for factors associated with late and non‐attendance. Results: For the first surveillance test, risk of non‐attendance was significantly higher in younger women, those without post‐secondary education, and non‐users of prescribed contraception. Factors significantly associated with late attendance for the first test were the same as for non‐attendance, plus current smoking and having children. The most important predictor of non‐attendance for the second surveillance test was late attendance for the first test (OR = 9.65; 95% CI, 6.60–16.62). Non‐attendance for the second test was also significantly higher among women who were younger, smokers and had negative cytology on the first surveillance test. Late attendance for the second surveillance test was higher in women who were younger, smokers, had children and attended late for the first test. Conclusions: Women at highest risk of default from follow‐up cytology tend to be young, smoke, lack post‐secondary education, and have defaulted from a previous surveillance appointment. Tackling default will require development of targeted strategies to encourage attendance and research to better understand the reasons underpinning default.     

Preparticipation screening—the way forward is smart screening

The image of a young athlete collapsing on the pitch, followed by resuscitation, leaves an unforgettable impression. However, this impression should not seduce us into resuscitating the debate for large-scale preparticipation screening without doing the smart thing: taking a step back to review what we know to be effective, and what has been shown not to be effective. What we should do is use this momentum to focus on what we still need to know.     

Hyperthermia in cervical cancer – current status

BackgroundThis article reviews the salient features of recent results of clinical studies. It puts a special emphasis on technical aspects, mechanisms of action together with radiotherapy and chemotherapy and points out areas for additional investigation.AimTo present the current state of knowledge on hyperthermia (HT) and to highlight its role in the treatment of cervical cancer.Materials and methodsThe literature on the clinical use of combined hyperthermia for cervical cancer was analyzed. Clinical outcomes together with the technical aspects and the role of HT were also evaluated.ResultsClinically randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in the treatment of cervical cancer without significant acute or late morbidities. The technological advances have led to an effective and safer treatment delivery, thermal treatment planning, thermal dose monitoring and online adaptive temperature modulation.ConclusionsDue to rapid development over the last decade of hyperthermia systems and new studies at the basic science and clinical level, the perception of hyperthermia as a part of multimodality treatment in cervical cancer has been changed. However, there is still a need for multicentre randomized clinical trials.