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Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers .With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid-beta (Aβ) positron emission tomography (PET) accumulation in non-demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein-derived three-range CSF cut-points to previously described binary ones.In our main longitudinal analyses, we highlight CSF p-tauThe proposed approach can refine clinico-biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker-related cognitive decline in comparison to binary cut-points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.

Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [We assessed cognitively unimpaired young, cognitively unimpaired, mild cognitive impairment and AD individuals with [The threshold for positivity was 15.085 pg/mL for plasma pTau181 and 17.652 pg/mL for plasma pTau231. Most individuals had concordant statuses, however, 18% of plasma181/PET, 26% of plasma231/PET and 25% of the pTau231/pTau181 were discordant. Positivity to at least one biomarker was often accompanied by diagnosis of cognitive impairment, Aβ positivity, APOEε4 carriership, higher levels of [Plasma pTau181, pTau231 and [Moreover, this study was supported by Weston Brain Institute, Canadian Institute of Health Research and Fonds de Recherche du Québec.

The human brain’s interregional communication is vital for its proper functioning. A promising direction for investigating how these regions communicate relies on the assumption that the brain is a complex network. In this context, images derived from positron emission tomography (PET) have been proposed as a potential source for understanding brain networks. However, such networks are often assembled via direct computation of inter-subject correlations, neglecting variabilities between subjects and jeopardizing the construction of group representative networks. Here, we used [18F]FDG-PET data from 1027 individuals at different syndromal stages (352 CU, 621 MCI and 234 AD) to develop a novel method for constructing stable (i.e. resilient to spurious data points) metabolic brain networks. Our multiple sampling (MS) scheme generates brain networks with higher stability when compared to the conventional approach. In addition, the proposed method is robust to imbalanced datasets and requires 50% fewer subjects to achieve stability than the conventional approach. Our method has the potential to considerably boost PET data reutilization and advance our understating of human brain network patterns in health and disease.

Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer's Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10-25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10-08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10-07, nearest gene=CYTIP). As the APOE e4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.

Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterised neurological syndromes involving the peripheral and central nervous system (n = 34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n = 94) and without (n = 24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with central nervous system inflammation (encephalitis and acute disseminated encephalomyelitis) (14800pg/mL [400, 32400]), compared to those with encephalopathy (1410pg/mL [756, 1446], peripheral syndromes (GBS) (740pg/mL [507, 881]) and controls (872pg/mL [654,1200]). Serum neurofilament light levels were elevated across patients hospitalised with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19., Graphical Abstract Graphical Abstract

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation. Hence, the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies. In this longitudinal study, we aim to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers. Methods: We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer’s Network according to their mutation carrier status. Regression mixed effect models with family-level random effects evaluated the interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age and estimated years of onset (EYO) as a function of metabolism measured by [18F]flurodeoxyglucose ([18F]FDG) positron emission tomography in DIAD mutation and non-mutation carriers. An exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Regression mixed effect models then evaluated the interactions of specific neuropsychiatric subsyndromes with EYO and age on metabolism. Results: 119 mutation and 102 non-mutation carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with greater global and regional [18F]FDG uptake decline in the posterior cingulate and ventromedial prefrontal cortices, bilateral parietal lobes and right insula in DIAD mutation carriers. The neuropsychiatric subsyndrome of agitation, disinhibition, irritability and depression interacted with EYO to drive [18F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [18F]FDG uptake in DIAD non mutation carriers. Conclusions: NPS in cognitively intact DIAD mutation carriers are clinical indicators of subsequent metabolic decline in brain networks vulnerable to AD. Our findings further advanced the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD.

Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.

Amyloid-β deposition into plaques is a pathologic hallmark of Alzheimer disease appearing years before the onset of symptoms. Although cerebral amyloid-β deposition occurs on a continuum, dichotomization into positive and negative groups has advantages for diagnosis, clinical management, and population enrichment for clinical trials.

STAGING In 2000 FIGO recommended a clinical staging of gestational trophoblastic tumors and requested that such cases should be reported to the Annual Report on the Results of Treatment in Gynecological Cancer. For this purpose the definitions of the clinical stages of gestational trophoblastic tumors are presented in Table 1. According to FIGO, hydatidiform mole should be registered but not be staged as Stage 0 because if hCG persists and the patient requires chemotherapy restaging would be required. Such restaging transgresses the basic principle of any staging system. Patients with hydatidiform mole are placed on record but staging only applies to trophoblastic neoplasia. Cases which do not fulfill the criteria for any given stage should be listed separately as unstaged. It should be realized that most cases of low risk metastatic disease are comprised by Stage III, while the high risk group of metastatic tumors first described by Hammond is the group that comes under Stage IV. In 2000 FIGO accepted the World Health Organization scoring system based on prognostic factors that were first devised by Prof. Kenneth Bagshawe. The score values for the risk factors will be 1, 2 and 4. Blood groups will not be used in the scoring system. Liver metastases will be given a score of 4. The cut-off score for low-risk and high-risk neoplasia was ratified by the June 2002 FIGO Committee on Gynecologic Oncology announcement. A score of 6 or less is low risk disease treatable by single agent chemotherapy. A score of 7 or greater is high risk disease that requires combination chemotherapy. Medium risk disease has been eliminated. This combining of the modified WHO risk factor scoring system with the FIGO staging was accepted by the FIGO Committee on Gynecologic Oncology in September 2000 and ratified in June 2002 with the FIGO announcement. It is now part of the FIGO staging and scoring system for gestational trophoblastic neoplasia.

The major task faced by a clinician having made a diagnosis of cancer is to determine the most effective therapy and formulate a prognosis for the patient. In order to optimally manage a cancer, both the extent of the disease and the knowledge of its biology are essential. The extent of the disease is generally expressed in terms of its stage. The major purpose of staging that has been agreed upon internationally is to offer a classification of a cancer’s extent so as to provide a method of conveying ones clinical experience to others for the comparison of treatment methods without confusion or ambiguity. Cancer staging is central to the modern management of cancer patients. Cancer is also a biologic continuum and a dynamic process, which is artificially compartmentalized by staging systems. It is clear, however, that the phases or sub-stages must have clinical relevance. Cancer staging systems should also be evidence-based and they should be user friendly. Staging systems need to be based on the best available knowledge at hand and this implies that the changes will occur over time based upon the development or the acquisition of new knowledge. It also follows that the acquisition of this knowledge is facilitated by the use of staging system insofar as staging will help with knowledge creation by facilitating clinical research, producing new data on similar groups of patients and also by integrating this new data about similar patients from diverse sources. Staging also helps knowledge dissemination by providing a common international language for information sharing and facilitates the teaching of both new and established health care workers. Gynecologists have a long and proud tradition of using staging systems for female cancers, dating back to the League of Nations staging system for cervical cancer, first published in 1920. In 1954 FIGO assumed the patronage of the Annual Report on the Treatment of Gynecological Cancer. With it also came the responsibility for overseeing the staging of gynecological cancers, which were at the heart of the Annual Report data and information system. Since that time the FIGO Oncology Committee has made several modifications to the various staging systems for gynecological cancer, most notably those for cervix and endometrial cancer. 1954 also saw the UICC set up a committee on clinical stage classification and applied statistics, which had as its aim the extension of the general technique of classification of cancer at all sites by anatomical extent of the disease using the TNM system. The FIGO system of classification was originally based on clinical examination, essentially of the anatomical extent of disease. Over the years all staging systems for gynecological cancers, with the exception of cervical cancer and gestational trophoblastic neoplasia, have moved from a clinical basis to one of a surgical pathological nature. The classification system and stage grouping, once established, must remain unchanged in medical records. Clinical stage is essential to select and evaluate therapy, while the pathological stage provides the most precise data to estimate prognosis and calculate end results. The FIGO and TNM classifications are virtually identical. The TNM Prognostic Factor Project Committee has graciously agreed to defer to all questions regarding staging of gynecological cancer to the FIGO Committee on Gynecologic Oncology. In conclusion, any good staging system must have three basic characteristics. It must be valid, reliable, and above all, it must be practical. Validity means that the staging system must allow for the creation of groups of cases, that experience similar outcomes at the same time reflecting a full range of possible presentations for each type of cancer. Also over time, the system in order to retain its validity must be flexible so that it can adapt to important changes in medical care. A reliable staging system should ensure that identical cases would always be assigned to the same stage category. It should be unambiguous; it should be based as far as possible on measurement quantities that have been evaluated objectively. The system should also not be subject to frequent changes until sufficient data and information is obtained to warrant such changes. Finally, a practical staging system must be suitable for day to day use in a wide range of clinical environments and must not require diagnostic procedures that are not readily available to most practitioners or extraordinary expertise or knowledge regarding a particular malignancy. The staging classification is reported at the beginning of each tumor site section, along with rules and recommendations.

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings.We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC).In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LR- were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LR- were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LR- were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LR- were 2.77 and 0.75, respectively.In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

BACKGROUND. Because 80% of cervical cancers arise in low-resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large-scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy. METHODS. Patients entered either a screening or diagnostic study of several optical technologies: quantitative cytology, quantitative histopathology, and fluorescence and reflectance spectroscopy using a point probe, a multispectral digital colposcope, or a combination of the two. We calculated sensitivities, specificities, positive and negative predictive values, and their confidence interval testing conventional cytology, Hybrid Capture (HC) II testing, and DNA ploidy measured on the Feulgen-stained quantitative Pap smear. RESULTS. The current investigation reports on 1555 patients for whom colposcopically directed biopsies were read 3 times by study pathologists. The final histopathologic diagnosis was high grade (cervical intraepithelial neoplasia [CIN] 2, CIN 3, carcinoma in situ [CIS], and cancer) in 16% of patients. Using high-grade squamous intraepithelial lesions (SILs) histopathology as the threshold and gold standard, the sensitivity and specificity, respectively, were: 0.47 and 0.96 for conventional cytology, 0.91 and 0.80 for HC II, and 0.59 and 0.93 for DNA ploidy. The positive and negative predictive values (PPV, NPV) for conventional cytology were 0.70 and 0.90, 0.46 and 0.98 for HC II, and 0.63 and 0.92 for DNA ploidy. CONCLUSIONS. DNA ploidy shows comparable sensitivity, specificity, PPV, and NPV values to conventional cytology and HC II. Unlike conventional cytology, DNA ploidy is semiautomated and can be performed in less than 8 hours. Cost effectiveness studies are under way, but in the authors' laboratory DNA ploidy is inexpensive. Cancer 2006. © 2006 American Cancer Society.

Objective To determine the probabilities of transition of stages in the natural history of cervical cancer by conducting a meta-analysis of published studies on the topic. Study Design We identified health states of interest in the natural history of cervical precancer, identified all possible papers that could meet selection criteria, developed relevance and acceptability criteria for inclusion, then thoroughly reviewed the selected studies. To determine the transition probability data we used a random effects model. Results We determined probabilities for 4 health state transitions. The 6-month mean predictive transition probability (95% confidence intervals with prediction interval in parentheses) for high grade squamous intraepithelial lesions (HSIL) to cancer was 0.0037 (0.00004, 0.03386), for low grade squamous intraepithelial lesions (LSIL) to HSIL was 0.0362 (0.00055, 0.23220), for HSIL to LSIL was 0.0282 (0.00027, 0.35782), and for LSIL to normal was 0.0740 (0.00119, 0.42672). Conclusion The transition probabilities between cervical cancer health states for 6-month intervals are small; however, the cumulative risk of cervical cancer is significant. Markers to identify the cervical precursors that will lead to the transition to cervical cancer are needed.

Objectives: To determine the factors that influence risk of cervical cancer after three consecutive negative Pap smears. Methods: A cohort study was conducted using data from the British Columbia Cervical Cancer Screening Program and British Columbia Cancer Registry. Analysis was based on a one percent sample of women aged 20-69 years with Pap smears enriched with all invasive cervical cancer cases diagnosed between 1994-99. Screening intervals, after three negative screens, were created with the following variables: age at beginning of interval, interval length, previous cytologic abnormality and previous cervical procedure. The risk of cervical cancer by histologic type was calculated using survival analysis methods. Results: The sample consisted of 10,509 women, who contributed 28,309 intervals, and 371 cervical cancer cases. The incidence rate of invasive squamous cervical cancer increased with time since last screen up to six years. Women with a history of dysplasia remained at elevated risk for squamous cancer, hazard ratio=2.6 (95% confidence interval [CI]=1.9, 3.4) but age or previous procedure were not related to risk. No relationship between time since last screen and non-squamous cancer risk was found although history of a previous procedure was significant. The marginal effectiveness of Pap smears declined with increasing frequency of use. Conclusions: This study confirmed the preventive effect of Pap smear screening and its dependency on frequency of use. Women with a history of dysplasia, prior to three consecutive negatives, were at increased risk of developing invasive squamous cervical cancer compared with women with no such history.

In 1991, FIGO added non-surgical-pathologic prognostic risk factors to the classic anatomical staging system. These include urinary hCG levels >100000mIU/ml and/or serum b-hCG >40000mIU/ml and the duration of an antecedent pregnancy being >6 months. Since gestational trophoblastic diseases (GTD) have a very high cure rate in virtually all patients, the ultimate goal of staging is to differentiate patients who are likely to respond to less intensive chemotherapeutic protocols, from those who will require more intensive chemotherapy in order to achieve remission. Staging should be based on history, clinical examination, and appropriate laboratory and radiological studies. Since hCG and b-hCG titers accurately reflect clinical disease, histologic verification is not required for diagnosis, although it may aid in therapy.

Primary site The vagina extends from the vulva upward to the uterine cervix. Cases should be classified as carcinoma of the vagina when the primary site of the growth is in the vagina. Tumors present in the vagina as secondary growths from either genital or extra-genital sites should be excluded. A growth that has extended to the portio and reached the area of the external os should always be allotted to carcinoma of the cervix. A growth limited to the urethra should be classified as carcinoma of the urethra. Tumor involving the vulva should be classified as carcinoma of the vulva. There should be histologic verification of the disease. Nodal stations The vagina is drained by lymphatics to the pelvic nodes in its upper two-thirds and to the inguinal nodes in the lower third. Metastatic sites The most common sites of distant spread include the lungs, liver and bony skeleton. The rules for staging are similar to those for carcinoma of the cervix.

Slow but steady progress has been made in the earlier diagnosis and better treatment of gynecological cancers, particularly over the last 50 years. Cervical cytology screening programs, where implemented, have led to a remarkable reduction in both the incidence and mortality from clinically invasive cervical cancer. This relatively simple technology has been truly one of the major success stories of modern medicine, but unfortunately this technique has not been uniformly applied to all women in the world, particularly to women in developing countries. New research into cervical cancer etiology, the role of HPV, and the development of vaccines against this virus offer a great hope particularly for developing countries. In addition, the combination of radiotherapy and chemotherapy has resulted in a marked improvement in outcome results for women with advanced cervical cancer. Ovarian cancer has seen the development of effective chemotherapy strategies for this disease. Currently this disease remains one of the major scourges in industrialized countries but the continued evolution of knowledge with regard to optimum sequencing of chemotherapeutic agents and surgery offers the prospect for better outcomes, less morbidity and a better quality of life. Ongoing research into the development of newer chemotherapeutic agents and a better understanding of the actual mechanisms regarding the efficacy of chemotherapy and drug resistance offers great promise for the future. Endoscopic surgery for staging and also for therapy shows promise for improved quality of life as well as outcomes for patients in the future and offers the challenge of trying to make this technology readily available to all women in the world. As we gain a better understanding of the molecular basis of disease and health we will truly be able to intervene in a preventive mode in the new millennium.

Organized cervical cancer screening services consisting of conventional Papanicolaou cervical smears, colposcopy, and related treatment modalities are readily available in all provinces. The purpose of this report was to study the impact of colposcopy usage and costs on cervical cancer incidence and mortality rates in several Canadian provinces. Knowledge of such information is essential before newer technology such as liquid-based cytology and human papillomavirus testing is introduced or replaces the traditional systems used.The Ministries of Health of five provinces were contacted and asked to furnish information on the number of colposcopic services and fee-for-service costs for these and for cryosurgery, carbon dioxide laser vaporization, loop electrosurgical excisions, and cold-knife conizations for the year 2000. Canadian Cancer Society estimates of incidence and mortality rates for cervical cancer were also obtained.All provinces had similar incidence and mortality rates for cervical cancer; however, the number of colposcopic services on a per-capita basis varied substantially, with Manitoba and Ontario having rates that were approximately two or three times higher. Fee-for-service payments for colposcopy were similar in the Provinces studied but unit costs for surgical treatment services were highest in Ontario and British Columbia.Although both the incidence and mortality rates for cervical cancer in Canada fell dramatically after the Walton Report in 1976, these rates have plateaued over the past decade despite widespread availability of colposcopy and related ambulatory treatment services. Higher rates of colposcopy usage do not seem to result in lower incidence rates for this disease. Unit costs for colposcopy are similar among the provinces reviewed, but substantial difference exists for certain treatment services. Additional studies are recommended before the widespread introduction or replacement of existing methods with newer, more costly techniques.

It is inaccurate to describe prostitution as a legal activity in Canada. It is an activity that is criminally prohibited indirectly rather than directly, making it illegal in almost all instances. Shannon [1][1] treats decriminalization as monolithic, when in fact Sweden and other Nordic countries

The purpose of this study was to document some of the results of a comprehensive provincial cytology and colposcopy program for the year 1988 and also to review the impact on the incidence and mortality rates for a clinical carcinoma of the cervix.This study is a retrospective analysis of the cytologic results of all patients examined provincially in 1988 and a review of the clinical records of patients diagnosed with invasive cancer and those who died of disease.In 1988 490,985 women (40% of all women over the age of 15 in the population) were screened, with 9.2% showing abnormal cells. A total of 79% of women screened were less than 50 years old and accounted for 86.3% of all abnormal smears. Women less than 35 years old were more likely than older women to have moderate dyskaryosis or worse.Intensive comprehensive cytology and colposcopy programs reduce not only the incidence and mortality of clinical carcinoma of the cervix but also rates of in situ disease and other precursors.

Objective: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. Materials and Methods: Screening (n = 835) and diagnosis (n = 518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR−), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. Results: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR− were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR− were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. Conclusions: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2865–71)

Objective The study was undertaken to provide consensus guidelines for the management of women with a cytologic interpretation of high-grade squamous intraepithelial lesion (HSIL) on cytologic examination. This review article presents relevant literature supporting the proposed guidelines. Participants An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology. Consensus process Guidelines for the management of women with HSIL cytologic results were developed through a multistep process. Draft management guidelines were developed by the HSIL working group after formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the American Society for Colposcopy and Cervical Pathology Consensus Conference, September 6 through 8, 2001, in Bethesda, Maryland, the guidelines were discussed, revised, and adopted by formal vote. Conclusions Evidence-based guidelines have been developed for the management of women with HSIL cytologic results.

Summary In a see-and-treat protocol, patients referred for colposcopy because of an abnormal Pap smear in cervical-cancer screening can be treated by loop excision, without biopsy, during one visit to the clinic. However, overtreatment in the see-and-treat strategy has been reported to be 1·2–83·3% for low-grade squamous intraepithelial lesions (SIL) and to be 13·3–83·3% for high-grade SIL. Range of overtreatment narrowed to 4·0–23·5% for those with normal pathology and to 18·0–29·4% for those with normal or low-grade pathology when calculation of overtreatment was restricted to patients diagnosed with high-grade SIL on colposcopy and referral Pap smear. Most common treatment complications are bleeding and infection. Nonetheless, the strategy has become accepted internationally: low costs, decreased patient anxiety, and increased compliance make it appealing, especially in settings with limited health resources, and for patients at risk of not being treated in a timely manner or of not returning for a second appointment. Mathematical modelling may give information about the appropriateness and usefulness of this treatment while the results of long-term clinical trials are awaited.

Rules related to staging: • Corpus cancer is now surgically staged, therefore procedures previously used for determination of stages are no longer applicable (e.g. the findings of fractional curettage to differentiate between Stage I and Stage II). • It is appreciated that there may be a small number of patients with corpus cancer who will be treated primarily with radiation therapy. In these cases, the clinical staging adopted by FIGO in 1971 would still apply, but designation of that staging system would be noted. • Ideally, width of the myometrium should be measured along with the depth of tumor invasion.

Primary site The Fallopian tube extends from the posterior superior aspect of the uterine fundus laterally and anteriorly to the ovary. Its length is approximately 10 cm. The lateral end opens to the peritoneal cavity. Metastatic sites Carcinoma of the oviduct can metastasize to the regional lymph nodes, including the para-aortic nodes. Direct extension to surrounding organs, as well as intraperitoneal seeding, occurs frequently. Peritoneal implants may occur with an intact tube.

Objective . To determine the diagnostic correlation between referral cytology, initial biopsies and colposcopic impression in patients assessed in a provincial cytology screening program. Methods . A retrospective review of the computerized cytology screening database for British Columbia (BC), to identify all patients having their first colposcopy between 1986 and 2000 in 24 participating clinics constituted the study population. 84,244 patient records were identified for analysis. Colposcopies were performed mainly by 37 general gynecologists as part of a province-wide colposcopy program. Correlation of cytology, colposcopic impression and directed biopsies was performed. Results . The colposcopic impression correlated with the referral cytology within one degree in over 90% of cases. Colposcopists felt cytology underestimated disease in 1.5% and overestimated disease in 8.3%. Cytology–histology correlation within one degree occurred in 82%. Cytology underestimated the result of the biopsies in 2.3% and appeared to overestimate disease in 16.1% of patients. Patients with HSIL cytology had corresponding lesions in 77%, with a further 4.9% having LSIL disease. The predictive accuracy of colposcopy increased with advancing severity of disease expected. As the degree of cytological abnormality worsened, the predictive accuracy of colposcopic diagnosis increased. Conclusions . Both cytology and colposcopy have high sensitivity but low to moderate specificity. Colposcopy is most accurate in identifying high-grade diseases. Colposcopic impression correlates closely with the cytology diagnosis and combining the two produces optimum results.

To estimate the quality of community colposcopic practice in British Columbia through an assessment of the degree of correlation between colposcopy, cytology, and histology.We reviewed all new-patient colposcopies in British Columbia during 2001 by 37 gynecologists in 24 hospital-based clinics.Colposcopic impression closely mirrored the referral cytology diagnosis in 89.8% of cases. As with cytology-biopsy comparisons, discordant cases were more likely to be overestimates of disease rather than underestimates, 18.8% versus 1.8%. Overestimates were usually biopsy sampling errors rather than false positive cytology. The overall correlation between cytology and biopsy was considered satisfactory in 79.4% of cases. Satisfactory agreement between the colposcopic diagnosis and accompanying biopsies occurred in 86.8% of patients. Five colposcopists had performance scores below this standard. Colposcopy with a sensitivity of 90.3% and a specificity of 57.3% as practiced in this provincial program would appear to be of a satisfactory level. The rate of intraepithelial or invasive disease increased from 40.6% in patients with low-grade squamous intraepithelial changes to 91.9% in patients with suspicious or malignant cytology. The value of the colposcopic impression to identify disease correlated best with the higher the grade of disease predicted (64.6% to 92.6%).A measure of the colposcopic proficiency in the community can be estimated by comparing the level of agreement between the presenting cytology, colposcopic impression, and corresponding directed biopsies. The results of this study would indicate that 5 individuals had practice standards that were below average. An integrated cytology-colposcopy program facilitates the assessment and identification of below-average practice standards in a community.

Strategies to modify risk for female or gynecological cancers will vary with our knowledge of the epidemiology, etiology, and specific molecular mechanisms for each individual cancer. In general, cancer preventive strategies have been divided into primary and secondary prevention with primary prevention directed toward the causative factors for a disease. Secondary prevention is classically used in cervical cancer cytology screening programs and is essentially an attempt to identify individuals in a population with preclinical phases of the disease where intervention will impact mortality the most. A vast literature has evolved regarding the epidemiology of most of the common cancers in women. While the specific molecular mechanisms are not completely understood at this time knowledge of contributing factors for many of these tumors is well known. The association of cigarette smoking with lung cancer has been well established and the increasing rates of lung cancer, particularly in women, are directly linked to the increasing number of female smokers in the population. Indeed in many western countries lung cancer deaths have overtaken breast cancer as the most common cause of death from malignant disease in women. Excessive sun exposure without adequate skin protection is another lifestyle activity that is related to the high incidence of skin cancer in certain areas. Epidemiologically, cervical cancer has been studied extensively with the current data indicating a causal role of exposure to human papillomavirus (HPV), particularly at an early age in this disease. Hereditary breast and ovarian cancer syndromes are well understood and as more information on human genomics becomes available a clear understanding of the underlying molecular mechanisms of these diseases will be possible and hopefully will result in effective strategies for their control. Unfortunately, in spite of the vast knowledge that is available regarding risk factors for many of these malignancies we have been unable to influence effective lifestyle changes that could substantially reduce the risk of these malignancies in our population. Increased efforts in education, research, and commitment--both financial and educational--are required by governments and other social organizations.

Primary site Cases should be classified as carcinoma of the vulva when the primary site of growth is in the vulva. Tumors present in the vulva as secondary growths, from either a genital or extra-genital site, have to be excluded. Malignant melanoma should be separately reported. A carcinoma of the vulva that extends into the vagina should be considered as a carcinoma of the vulva. There must be histologic confirmation of the cancer.