The characteristics of false negative cervical smears--implications for the UK cervical cancer screening programme

OBJECTIVE: To accurately determine whether there are any features of an abnormal cervical smear that predispose to the production of a false negative report, in order to gain insight into why false negative reports are issued, and to establish whether there are steps that can be taken to reduce them. DESIGN: A quantitative retrospective analysis using the AxioHOME microscope of the number, size, and spatial distribution of abnormal cells in a set of 50 slides comprising a mixture of false negative and true positive cervical smears. SETTING: Five different cytology laboratories in the United Kingdom. RESULTS: False negative smears were found to be quantitatively different from true positive smears. They contained significantly fewer abnormal cells (median number of abnormal cells for false negatives = 173, median number of abnormal cells for true positives = 1712; p < 0.004), and these were more likely to be unevenly distributed on the slide. It was possible to predict with a high degree of accuracy whether a smear was a false negative by analysing number and distribution alone (kappa = 0.57). CONCLUSIONS: False negatives are quantitatively different from true positive cervical smears. This has important implications for quality assurance in the UK cervical screening programme. More consideration needs to be given to the effectiveness of existing quality assurance measures, which need to be tailored to the preferential detection of this type of abnormal cervical smear.     

Implementing targeted cervical cancer screening videos at the point of care

Objective

To develop and implement educational videos to improve cervical cancer health literacy for patients within a safety net healthcare system.

Methods

Testimonial-style videos were developed with the goal of describing the Pap test to low literacy patients and motivating them to participate in regular cervical cancer screening. Nurses were trained to use the electronic medical record to identify patients due or past due for a Pap test according to the current screening guidelines. They played the video for all eligible patients as they waited to be seen by their physician in clinical examination rooms.

Results

Four 2-minute videos were developed in English, Spanish, and Vietnamese. Videos were made available on desktop computers in 458 exam rooms at 13 community health centers.

Conclusion

Integration of educational videos into the workflow of high-volume community health centers is feasible. Future work will focus on optimizing uptake of the videos as well as assessing their efficacy for improving cervical cancer health literacy.

Practice Implications

Integrating targeted videos into patient flow may be a feasible way to address health literacy barriers to cervical cancer screening within a busy workflow environment.     

Faculty expectations and primary care residents' perceptions concerning residents' growth in competence at one medical school.

The authors studied at one school both the developing confidence of primary care residents and the expectations of both internal medicine and specialty faculty members regarding the abilities of the residents. From 1980 to 1988, residents in the study institution's program in internal medicine primary care completed self-assessments concerning their diagnostic and management skills in primary care and several specialties at the start of their training and at the ends of their first, second, and third years. In 1988, the authors elicited the expectations of the primary care and specialty faculties regarding the levels of competence that residents should achieve in the specialties by the end of their third year. When the faculty assessments were compared, the specialists were found to ascribe greater levels of autonomy to residents. The authors conclude that involving residents and faculty members from various disciplines in developing expectations and evaluation criteria can enhance faculty members' perceptions of residents' clinical competence and residents' achievement of it.     

Tailored messages for breast and cervical cancer screening of low-income and minority women using medical records data

Barriers to screening and early detection often result in cancers in low-income and minority women diagnosed at stages too advanced for optimal treatment. This randomized controlled trial examined whether a personalized form (PF) letter containing generic cancer information and a personalized tailored (PT) letter containing minimally tailored individualized risk factor information based on medical records data affected breast and cervical cancer screening among 1574 urban low-income and minority women. The personalized form-letter group was significantly more likely to schedule a screening appointment and to have undergone a Pap test and mammography within 1 year after the intervention than were the tailored letter and control groups (P<0.001 for all comparisons). Personalized tailored letters that contain individualized cancer risk factor information may decrease the likelihood of receiving cancer screening among medically underserved low-income and minority women, but personalized form letters that contain generic cancer information may improve these rates in this disadvantaged population.     

Comparison of the performance of paired urine and cervical samples for cervical cancer screening in screening population

The main objective of this work is to determine the performance of urine for human papillomavirus (HPV) detection in cervical cancer screening in screening population. Paired urine and cervical samples were collected from 2038 women (careHPV group: 1002, cobas4800 group: 1036) in 2015. Urine was tested by a new urine-based HPV test and cervical samples by careHPV or cobas4800 HPV test. Women were triaged based on cervical results and then referred to colposcopy with biopsy as clinically indicated. In 2017, women were followed up and screened with cotesting strategy, women with any positive would be referred and biopsied if necessary. In careHPV group, the HPV prevalence of urine was 14.1%, and 16.4% for cervical samples. In cobas4800 group, it was 19.1% and 20.4%, correspondingly. The concordance of urine samples compared with cervical samples was moderate (careHPV group: 86.6%; κ = 0.48; cobas4800 group: 83%; κ = 0.46). The baseline sensitivity and specificity for urine against CIN2+ detection were 85.7%, 86.8% in careHPV group, and 69.2%, 82.3% in cobas4800 group, respectively. Cervical samples were 100% sensitive for both tests (careHPV and cobas4800) and 85.2% specific in careHPV group and 81.9% specific in cobas4800 group, respectively. The corresponding cumulative sensitivity and specificity were 68.8% and 87.1%, 58.8% and 81.9%, 87.5% and 85.5%, and 94.1% and 81.4%. Urine demonstrated certain potential in cervical cancer screening and could be an alternative if no better screening strategies available.     

Problems of cervical cancer screening programmes

The feasibility of using an age-sex register as a basis for a cervical cancer screening programme was investigated in a London practice serving both inner city and suburban populations. Only about 25% of 810 women aged 35-59 years who had not recently been screened responded to an invitation to attend a practice well woman clinic for a cervical smear. Nearly 30% of the invitations were returned `not known at this address' and there was no reply from the remaining 45%. A high proportion of incorrect addresses considerably reduces the effectiveness of a cancer screening programme based on an age-sex register covering an area with a mobile population and also makes it difficult to follow up women with abnormal smears adequately. Opportunistic screening remains essential and every effort should be made to encourage women to be responsible for their own cancer screening programmes.     

Diagnosis analysis in breast cancer and cervical cancer screening

Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance.     

Experiences in providing a screening service for colorectal cancer from a pathology laboratory

AIM: To provide a colorectal cancer screening service for the general public, based on the detection of blood in faeces, that was effective, affordable and convenient. METHODS: Kits for collecting faecal specimens were sold directly to the public and, after collecting three specimens, kits were transported to the laboratory for testing by an immunochemical procedure involving a positive cut-off value. Reports were sent to participants and their nominated doctors who were requested to provide information on participants testing positive. RESULTS: Over a 10-year period, 35 139 kits were analysed and 5.63% were positive. After follow-up, 7.4% of positive testing participants were found to have colorectal cancer, 23.4% adenomas, 34.6% miscellaneous non-neoplastic pathology and in 25.0% no abnormality was found. Sixty-six per cent of cancers were early stage, Dukes stages A and B. There were 35 139 kits processed on 16 240 individuals, indicating that a number were repeat testing. CONCLUSIONS: The screening service was able to detect a high yield of colorectal pathology, especially early stage neoplasia which is curable, and encouraged repeat testing. Education of doctors about how to investigate a positive test, and of participants about symptoms, have been important lessons arising from this screening service.     

Understanding the role of reactions to race-based treatment in breast and cervical cancer screening

Racial and ethnic disparities in breast and cervical cancer mortality persist despite effective screening methods. We examined associations between race/ethnicity and Pap testing within three years or mammography within two years, controlling for a composite reactions-to-race-based-treatment variable created using data from the 2002 and 2004 Behavioral Risk Factor Surveillance System Reactions to Race module, which assessed respondents experiences based on one's race. We calculated prevalence of Pap testing (for women aged > or = 18) and mammography (for women aged > or = 40) by race, and fit logistic regression models to estimate the strength of association of reactions to race-based treatment with screening and race--before and after controlling for demographics, socioeconomic status, health status, smoking and healthcare access. In the reduced model, black women were more likely (2.03: 95% CI: 1.55-2.65) to be screened for cervical cancer than whites. Reactions to race-based treatment did not impact the odds of black women receiving Pap tests or mammograms. Given current racial and ethnic disparities in breast and cervical cancer mortality, we suggest that more attention needs to be focused on follow-up of abnormal results and state-of-the art treatment for black and Hispanic women.     

Improving the effectiveness of cervical cancer screening

A review of 100 cases of invasive cervical cancer was designed to assess what changes in cervical screening services might be most effective in reducing mortality. In 68 cases there had apparently never been screening: no system of individual invitation existed for unscreened women. In 10 cases the last smear was reported as normal over five years earlier: a five-year recall system existed but was inefficient. In 13 cases suspicious cervical smear reports had not been followed up adequately. Two cases might have been diagnosed earlier, in spite of `normal or inflammatory' smears, if the symptoms had been fully elicited. For the remaining seven cases one or more smear was reported as normal within five years of diagnosis of invasive cancer. Overall, 15 cases might have been picked up earlier if suitable opportunities for screening which did arise had been exploited. It was concluded that a substantial proportion of these 100 women might have received treatment at an earlier stage solely by the rigorous implementation of the present screening policy.     

Primary HPV-based cervical cancer screening in Europe: implementation status,challenges, and future plans

BackgroundCytology-based screening has been a cornerstone of cervical cancer prevention for decades. Following extensive evidence demonstrating higher sensitivity and accuracy, lower variability and better reproducibility of human papillomavirus (HPV)-based screening compared with conventional or liquid-based cytology, recent European guidelines strongly recommend primary HPV-based screening over standard cytology-based screening. In addition, HPV-based screening offers the possibility of self-sampling and makes possible longer screening intervals in women with negative screening results.ObjectivesWe summarize the current status of implementation of HPV-based screening in Europe, describe the real-life experience and challenges from countries already performing HPV-based screening, and briefly review immediate and long-term plans for screening implementation in selected European countries.SourcesData were obtained from peer-reviewed literature, personal communication with experts and authorities involved in formulating national recommendations and practical guidelines, and relevant national websites.ContentAs of July 2019, the Netherlands and Turkey are the only European countries with fully implemented national HPV-based cervical cancer screening. Italy, Sweden and Finland have already implemented HPV-based screening in several regions, and several other countries are at various stages of implementation. Some countries are considering transitioning from cytology-based to HPV-based screening, but are struggling with the suboptimal performance of current population-based programmes. Implementation of HPV-based screening has resulted in higher colposcopy referral rates, but also higher detection rates of CIN3+ lesions and cervical cancers requiring immediate treatment. Cytology is mostly used as a triage test, although other strategies are under consideration in some countries.ImplicationsHPV-based screening is best suited in organized population-based screening settings. In 2019, cervical cancer screening policies across Europe vary greatly. Experience in countries with national and regional HPV-based screening already implemented is generally very positive. Urgent action is needed in many European countries, especially those with suboptimal opportunistic cytology-based cervical cancer screening.