Type 1 and type 2 cervical carcinomas: some cervical cancers are more difficult to prevent with screening

Although the Papanicolaou (Pap) smear is medical history's most successful cancer screening test, some cervical cancers are more difficult to prevent with screening than others. Cervical cancers that are difficult to prevent are seen disproportionately among interval cancers arising in previously screened women and in Pap test litigation. These include (i) rapidly progressing cervical cancers; (ii) cervical cancers in younger women; (iii) glandular cervical cancers; and (iv) cervical cancers in elderly women. Screening protocols have generally been designed to optimize prevention of slower-growing cervical squamous carcinomas in middle-aged women. To focus further attention on the heterogeneous screening challenges posed by different cervical cancers, we designate the more screening preventable majority as type 1 cervical cancers and the more difficult to prevent minority as type 2 cervical cancers. We review available data on why some cervical cancers are more difficult to prevent with screening and newer methods that may improve prevention.     

Liquid-based cytology for cervical screening

England and Wales' new National Institute for Clinical Excellence (NICE) has completed the first of its appraisals and issued guidance on a diagnostic technique rather than a therapeutic intervention. ¹ It was directed to examine the use of liquid-based cytology (LBC) for cervical screening and took evidence from a wide variety of sources. LBC is a new method of preparing cervical samples for cytological examination. Unlike the conventional 'smear' preparation it involves making a suspension of cells from the sample and this is used to produce a thin layer of cells on a slide.     

Preventive and therapeutic vaccines for human papillomavirus-associated cervical cancers

'High risk' genotypes of the human papillomavirus (HPV), particularly HPV type 16, are the primary etiologic agent of cervical cancer. Thus, HPV-associated cervical malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. Sexual transmission of HPV may be prevented by the generation of neutralizing antibodies that are specific for the virus capsid. In ongoing clinical trials, HPV virus-like particles (VLPs) show great promise as prophylactic HPV vaccines. Since the capsid proteins are not expressed at detectable levels by basal keratinocytes, therapeutic vaccines generally target other nonstructural viral antigens. Two HPV oncogenic proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are coexpressed in the majority of HPV-containing carcinomas. Therefore, therapeutic vaccines targeting these proteins may provide an opportunity to control HPV-associated malignancies. Various candidate therapeutic HPV vaccines are currently being tested whereby E6 and/or E7 are administered in live vectors, in peptides or protein, in nucleic acid form, as components of chimeric VLPs, or in cell-based vaccines. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic vaccine clinical trials. Should they fulfill their promise, these vaccines may prevent HPV infection or control its potentially life-threatening consequences in humans.     

Procedure for neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency

The value of screening of neonates for congenital adrenal hyperplasia is not universally accepted. Procedures for screening are recommended here in order to provide a structure to the testing and ultimately bring together data that will allow the effect of screening to be judged for benefit or dismissed as no better than clinical recognition of the disease state.     

ENCAPP: elastic-net-based prognosis prediction and biomarker discovery for human cancers

Background

With the explosion of genomic data over the last decade, there has been a tremendous amount of effort to understand the molecular basis of cancer using informatics approaches. However, this has proven to be extremely difficult primarily because of the varied etiology and vast genetic heterogeneity of different cancers and even within the same cancer. One particularly challenging problem is to predict prognostic outcome of the disease for different patients.

Results

Here, we present ENCAPP, an elastic-net-based approach that combines the reference human protein interactome network with gene expression data to accurately predict prognosis for different human cancers. Our method identifies functional modules that are differentially expressed between patients with good and bad prognosis and uses these to fit a regression model that can be used to predict prognosis for breast, colon, rectal, and ovarian cancers. Using this model, ENCAPP can also identify prognostic biomarkers with a high degree of confidence, which can be used to generate downstream mechanistic and therapeutic insights.

Conclusion

ENCAPP is a robust method that can accurately predict prognostic outcome and identify biomarkers for different human cancers.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1465-9) contains supplementary material, which is available to authorized users.     

Model program for screening oral cancers in the Roma population

Oral cancer has been identified as a significant public health threat. It is reported that about 3,800 new cases of oral cancer are diagnosed in Hungary each year with approximately 1,700 associated deaths. Oral cancer is the 6th most common cancer in men. Most oral cancers are preventable; 75% of oral cancers are related to tobacco use, alcohol use, or use of both substances together. While there is insufficient evidence to support or refute the use of visual examination as a method of screening for oral cancer in the general population, screening in high-risk populations is highly recommended. It was presumed that high-risk behavior including tobacco and alcohol use is one of the characteristics of Roma people. The main aim of the study was to elaborate a screening model program for the Roma population to determine risk factors of oral cancer and establish early diagnosis hence to reduce morbidity and mortality. In the program we planned to survey the risk factors in the target population, establish the diagnosis of oral cancer and/or pre-cancer and direct the patients to health care facilities. First we determined the target population in four Hungarian towns with the help of Roma social workers and local public health officers. We assembled a questionnaire on risk factors. Training for Roma social workers and screening personnel was also accomplished. Screening for oral precancerous lesions and cancer and survey the risk factors in the target population were performed at the same time. Patients screened to be positive were referred to specialists. Altogether 1,146 persons, 656 male and 490 female (age 20-77 years, mean 40 years), participated in the screening; 84% of them reported on some kind of complaints. We have got valid data on risk factors in connection with oral cancer. More than fifty percent of participants did not clean their teeth regularly, 75% were smokers, while 45% drunk alcohol regularly. 1,6% of screened participants had oral lesions that did not require referral to a specialist, while 2.3% of the screened subjects had referable oral mucosal lesions including leukoplakia. The overwhelming majority (93%) of participants screened to be positive did not see dentist regularly. As a conclusion, we elaborated a screening model program, which is applicable for disadvantaged (e.g. Roma) population to determine risk factors of oral cancer and establish early diagnosis hence to reduce morbidity and mortality. We surveyed the risk factors in the target population, established the diagnosis of oral cancer and/or pre-cancer lesions and directed the patients to care facilities. We also assisted them to get appropriate long-term care and follow-up. The importance of screening activities targeted on high-risk population was underlined.     

Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical cancers

Summary Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correlation between microvessel counts and COX-2 levels in uterine cervical cancers. COX-2 localized in the cancer cells, but not in the stromal cells of uterine cervical cancer tissues. COX-2 levels increased with advancement, and the prognosis of the 30 patients with high COX-2 expression in uterine cervical cancers was poor (60%), while the 24-month survival rate of the other 30 patients with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX-2 might work on angiogenesis in advancement. Therefore, long-term administration of COX-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced uterine cervical cancers.     

What does airport baggage screening have to do with cervical cancer screening?

The implementation of liquid based technologies for cervical cytology has delivered many of the expected benefits but is also accompanied by a raft of new challenges for the cytomorphologist. Differences in the presentation of cellular material may on occasion make it more difficult to detect subtle or scanty abnormalities and novel cellular appearances expand the existing list of differential diagnoses. This presentation will focus on these changes and will examine strategies which may assist the practitioner in the reliable reporting of cervical samples.     

HPV testing for cervical cancer screening in Croatia

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.     

A screening system for cervical cancer cytology.

A system for screening cervical cytological preparations is described which employs the Leitz Texture Analyzer System (E. Leitz, Rockleigh, N. J.) quantitative staining with acridine orange, and a fluorescence standard. The instrumentation scans cells on microscope slides and detects objects which it interprets to be nuclei with excess total nuclear green fluorescence intensity (Previous results employing manual measurements have indicated that normal nuclei do not produce total nuclear green fluorescence greater than a specific absolute intensity level). Detected objects are identified by visual observation. Cells (102,000) from 65 patients (29 normal, 36 abnormal) have been examined. In each abnormal sample, at least one abnormal cell was detected. In over half of the samples, three or fewer other objects (e.g. clumps of polymorphonuclear leukocytes) were detected. These are easily distinguishable from single nuclei, and could be discarded by someone with minimal cytological training.