Outcome and diagnostic reproducibility of the thyroid cytology "indeterminate categories" SIAPEC/SIE 2014 in a consecutive series of 302 cases.

PURPOSE: The clinical impact of the SIAPEC/SIE 2014 classification for thyroid cytology has been addressed in few studies that evaluated the malignancy rate and the relative prevalence of each category. No study analyzed its intra-observer and inter-observer reproducibility, so far. METHODS: We retrospectively collected all "indeterminate" lesions diagnosed before (2011-2014) and after (2015-2018) the application of the SIAPEC/SIE 2014 classification at our Institution. Their relative malignancy risks were calculated based on available histological diagnoses. Cytological and clinical features of TIR3A were compared with the surgical outcome. Finally, a large set of samples was re-evaluated in blind of the original cytological and histological diagnoses by two pathologists, independently. RESULTS: The prevalence of "indeterminate" diagnoses increased in years 2015-2018 (302/1482, 21% with 14% of TIR3A and 7% TIR3B categories) compared to years 2011-2014 (261/1680, 16%). Surgery was performed in 27% TIR3A and in 97% TIR3B cases. Malignancy rates were 40% for TIR3B and 17% for TIR3A, but were greatly influenced by the adoption of the WHO 2017 re-classification of encapsulated follicular-patterned lesions (decreasing to 28% and 6%, respectively). No criteria except for tumor size were associated to malignancy in TIR3A category. Intra-observer agreement of the experienced pathologist was 122/141 (86%), whereas inter-observer agreement between the expert and in-training pathologist was 95/141 (67%). CONCLUSIONS: In this real-life experience, the sub-classification of TIR3A and TIR3B slightly increased the overall prevalence of "indeterminate" diagnoses. Malignancy rates were higher than estimated for both TIR3A and TIR3B categories. Agreement among observers highly depended on pathologist's training.

Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center.

BACKGROUND: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.

Papillary glioneuronal tumors: Distinctive cytological characteristics and cyto-histologic correlation.

Intraoperative cytological examination and cyto-histologic correlation of papillary glioneuronal tumors have rarely been described in detail in the literature. A 23-year-old female presented at our institution with seizure-like activity, and a 3.0 cm left temporal lobe hypoattenuating lesion. She was accurately diagnosed with papillary glioneuronal tumor on Intraoperative cytology. The patient subsequently proceeded to stealth-guided awake left temporal craniotomy, confirming the diagnosis. In this article, we present a detailed report of papillary glioneuronal tumor (extremely rare central nervous system neoplasm) describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature.

Surveillance patterns of cervical cancer patients treated with conization alone.

OBJECTIVES: To determine surveillance patterns of stage I cervical cancer after cervical conization. METHODS: A 25-question electronic survey was sent to members of the Society of Gynecologic Oncology. Provider demographics, surveillance during year 1, years 1-3, and >3 years after cervical conization, use of pelvic examination, cytology, Human papillomavirus testing, colposcopy, and endocervical curettage were queried. Data were analyzed. RESULTS: 239/1175 (20.1%) responses were collected over a 5-week study period. All providers identified as gynecologic oncologists. During year 1, 66.7% of providers perform pelvic examination and 37.1% perform cytology every 3 months. During years 1-3, 61.6% perform pelvic examination and 46% perform cytology every 6 months. At >3 years, 54.4% perform pelvic examination every 6 months and 43% perform annual pelvic examination. 66.7% of respondents perform cytology annually, and 51.9% perform annual Human papilloma virus testing. 85% of providers do not offer routine colposcopy and 60% do not offer endocervical curettage at any point during 5-year follow-up. 76.3% of respondents screen patients for Human papilloma virus vaccination. CONCLUSIONS: To date, there are no specific surveillance guidelines for patients with stage I cervical cancer treated with cervical conization. The most common surveillance practice reported is pelvic examination with or without cytology every 3 months in year 1 and every 6 months thereafter. However, wide variation exists in visit frequency, cytology, and Human papillomavirus testing, and there is a clear trend away from using colposcopy and endocervical curettage. These disparate surveillance practices indicate a need for well-defined, uniform surveillance guidelines.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Distribution of breast lesions diagnosed by cytology examination in symptomatic patients at Eritrean National Health Laboratory, Asmara, Eritrea: a retrospective study.

BACKGROUND: Fine needle aspiration cytology is a simple, relatively accurate, non-invasive, and cost-effective method of diagnosing most breast pathologies. To date, there is no sufficient data depicting the distribution of breast lesions detected by fine needle aspiration cytology in our healthcare setting. The aim of this study was to elucidate the general distribution of breast lesions diagnosed by cytology test at Eritrean National Health Laboratory. METHODS: This retrospective study was carried out on 905 symptomatic patients between the years 2013 and 2017 at Eritrean National Health Laboratory. Diagnosis was made by fine needle aspiration cytology in patients with palpable breast lump and in some patients direct smear was prepared from a nipple discharge. Statistical analysis was carried out using Statistical Package for the Social Sciences version 23. RESULTS: A total of 905 patients were included in the study, of whom 871 (96.24%) were females. The age range of patients was from 13 to 93 years with mean and standard deviation of 33 ± 14.9 years. Breast lump, occurring in 892 (98.56%), was the most frequent presenting symptom. Fibroadenoma and fibrocystic breast lesions were the most prevalent lesions accounting for approximately 40% and 15%, respectively. Malignant breast lesions were seen predominantly in females above the age of 40 years with the highest frequency observed in the age range between 51 and 60 years. Pearson Chi-squared test showed significant association between patients' age above 40 years and the risk of having a malignant breast lesion (p < 0.001). The highest number of benign and malignant breast lesions was documented in 2014 with little fluctuation elsewhere in the study period. CONCLUSION: Fine needle aspiration cytology is a procedure of choice for preoperative diagnosis in breast lesions mainly in a resource-limited settings. Our study identified the occurrence of malignant breast lesions in young women, which is of a paramount public health concern. Of note, significant proportion of patients were late to seek medical attention. Therefore, enhancement of community awareness regarding breast disease and implementation of screening programs are necessary to ameliorate the morbidity and mortality associated with the disease.

Cytotechnologists' education and work in Finland.

OBJECTIVE: The aim of this study was to survey the work that cytotechnologists carry out in Finland. METHODS: An electronic questionnaire was planned with the Board of the Finnish Association of Cytotechnologists and an email containing the link was sent to all 107 of its members in January 2018. It included 17 questions on their age and work experience, education and work. There was also space for them to add other comments. RESULTS: Just under half (45%) replied. Their average age was 51 years (range 28-64), 41% had a Bachelor's degree, 59% had college-level training and they had spent an average of 15 years screening cytology specimens. After basic professional education, they had completed their cytology education in many ways and the most common routes were internship training (71%) and 1-year cytology specialisation (38%). Most of the cytotechnologists (85%) had duties other than screening and they mostly included a combination of histotechnology and cytotechnology (37.5%) or just cytotechnology (17%) or histotechnology (9%). The other 15% only screened cytology specimens. All cytotechnologists screened Papanicolaou smears, 94% screened urinary and respiratory specimens, 82% screened effusions and 39% screened fine-needle aspirations. CONCLUSIONS: We found that internship training provided essential training for Finnish cytotechnologists after they complete their basic professional studies. They reported many other duties in addition to microscopy screening.

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis.

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were carried out to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan. Ovid Medline and Ichushi-Web databases were searched from inception through to May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis. The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% confidence interval [CI], 0.18-1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI, 0.00-0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on four direct and nine comparative studies, showed no significant difference (summary odds ratio = 3.5 × 10-2 favoring LBC [95% CI, 6.9 × 10-4 -1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests. In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.

The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the published evidence for the use of oral brush cytology for the early detection of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: Literature was systematically searched through several databases: MEDLINE, EMBASE, PubMed, SCOPUS, Cochrane Library, and Web of Science. Additional review was performed through cross-checks on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of oral brush cytology on human tissues and its applications in the diagnosis, screening, or surveillance of oral cancer or OPMDs. RESULTS: The search strategy resulted in 343 abstracts or full-text articles, of which 36 met the inclusion criteria. The year of publication ranged from 1994 to 2017, and a total of 4302 samples from OPMDs, oral squamous cell carcinoma, and healthy controls have been investigated. Baby toothbrush, cytobrush, OralCDx® , and Orcellex® are the brushes that were used to obtain transepithelial mucosal samples for conventional and liquid-based cytology evaluation. CONCLUSIONS: Findings from this study indicate that meaningful evidence-based recommendations for the implementation of a minimally invasive technique to be utilized as an adjunctive tool for screening and early detection of oral cancer and OPMDs are complicated from the reported studies in the literature. There is need for well-designed clinical studies to assess the accuracy of oral brush cytology utilizing validated cytological assessment criteria for the diagnosis and prediction of OPMDs.

Predictors of abnormal cytology among HPV-infected women in remote territories of French Guiana.

BACKGROUND: Cervical cancer prevention using cervical cytology is insufficiently sensitive, a significant proportion of HPV-infected women having normal cytology. The objective of the present study was to try to identify factors associated with abnormal cytology in HPV-infected women living in remote areas of French Guiana. METHODS: A study was conducted in women aged 20-65 years having HPV infections confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV testing, cytology was performed and classified as normal or abnormal. Demographic and life history variables, and infecting genotypes were compared between the normal and abnormal cytology groups. RESULTS: None of the demographic and life history variables were associated with cytology results. HPV genotype 53 was significantly associated with absence of cytological abnormalities whereas HPV 52, 58, 16 and perhaps 33 and 66 were independently associated with a greater risk of cytological abnormalities. When grouping HPV genotypes in different species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly associated with abnormal cytology AOR = 5.1 (95% CI = 2.3-11.2), P < 0.001. CONCLUSIONS: It was not possible to predict which HPV-infected women will have cytological abnormalities or notfrom anamnesis. In this study HPV 53 seemed more benign than other HPV genotypes. On the contrary, species n°9, containing 5 of the genotypes contained in the nonavalent HPV vaccine, was significantly associated with more cytological abnormalities. HPV testing and vaccination with the nonavalent vaccine should be implemented in these remote parts of French Guiana.

Prevalence and determinants in cytology testing for cervical cancer screening in Spain (2006-14).

Background: Cervical cancer has decreased in developed countries thanks to cytology screening programmes. The aims of this study were To analyse the frequency and evolution of performing cytology tests and to determine the variables that influence their use. Methods: Cross-sectional study of non-institutionalized women who participated in the national health survey (2006, 2011/12) and the European Health Survey in Spain (2009, 2014). Study variables: cytology-testing, time since last cytology-test, reason for performing the test, age, nationality, marital status, social status, education level and place of residence. Results: The study evaluated 53 628 women in Spain over 15 years old, with a mean age of 52.68 (SD ± 19.12). About 94.1% were Spanish, 49.2% were married and 77.2% lived with a partner. In 2014, 72% had a cytology test, a number that increased significantly. Women aged 25-65 were 5.13 times more likely to undergo a cytology test than those aged 15-24 years old (odds ratio (OR): 5.13; P < 0.001); women with university educations were 9.23 times more likely to undergo a cytology test than those without university educations (P > 0.001); those of social classes I and II (high) were 1.2 more likely to undergo a cytology test than those of low social class (P = 0.026); and Spanish women were 1.74 times more likely to undergo a cytology test than foreigners living in Spain (P < 0.001). Conclusion: Frequency of cytology testing has increased in the last few years. Screening for cervical cancer is associated with higher social status, education level, age, and not being foreign.

Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. PATIENTS AND METHODS: Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. RESULTS: PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. CONCLUSIONS: Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.

Interobserver variance in myelodysplastic syndromes with less than 5 % bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2 % blasts.

Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2- < 5 %. This distinction is critical for establishing prognosis, but the reproducibility of this threshold is still not demonstrated. The objectives of our study were to explore the reliability of the 2008 WHO classification, regarding unilineage vs. multilineage dysplasia, by reviewing 110 cases previously diagnosed with MDS, and to study whether the threshold of ≤2 % BM blasts is reproducible among different observers. We used the same methodology as in our previous paper [Font et al. (2013) Ann Hematol 92:19-24], by encouraging investigators to include patients with <5 % BM blasts. Samples were collected from 11 hospitals and were evaluated by 11 morphologists. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. Discordance was observed in 36/108 suitable cases (33 %, kappa test 0.503). Diagnosis of MDS with unilineage dysplasia (refractory cytopenia with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS) or unclassifiable MDS) was assessed in 33 patients, by either of the two observers. We combined this series with the cases with RCUD or RARS included in our 2013 paper, thus obtaining 50 cases with unilineage dysplasia by at least one of the observers. The whole series showed very low agreement regarding RCUD (5/23, 21 %) and RARS (5/28, 18 %). Regarding BM blast count, the threshold of ≤2 % was not reproducible (discordance rate 32/108 cases, kappa test 0.277). Our study shows that among MDS WHO 2008 categories, interobserver discordance seems to be high in cases with unilineage dysplasia. We also illustrate that the threshold of ≤2 % BM blasts as settled by the R-IPSS may be not easy to reproduce by morphologists in real practice.

Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques.

BACKGROUND: Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. METHODS: AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. RESULTS: The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.

Incidence and prognostic significance of positive peritoneal lavage in colorectal cancer.

PURPOSE: The significance of peritoneal lavage cytology as a prognostic marker has been examined in various types of cancer. However, the meaning of positive peritoneal lavage cytology in colorectal cancer is still controversial. The aim of this review is to evaluate the prognostic significance of positive peritoneal lavage cytology in colorectal cancer. METHODS: An English literature search was performed on all studies published between 1998 and 2014 that compared the detection of peritoneal free cancer cells with survival or recurrence. RESULTS: Eighteen articles met the inclusion criteria. All studies employed one (or more) of the three techniques used to detect free cancer cells in the peritoneal cavity: (1) conventional cytology, (2) immunocytochemistry or (3) polymerase chain reaction. The incidence of positive peritoneal lavage cytology ranged from 2.2 to 47.2% across the studies. The factors correlated with positive peritoneal lavage cytology were tumor penetration and metastases (lymph node, liver and peritoneum). In nine studies, positive lavage findings were associated with a worse survival, and it was associated with increased recurrence in 13 studies. CONCLUSION: Positive peritoneal lavage cytology seems to be an indicator of a poor prognosis in colorectal cancer patients. Further studies are needed to clarify the prognostic impact of peritoneal lavage cytology, by comparing the different methods used for the collection of the peritoneal lavage.

2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease.

Cytology use for cervical cancer screening in Portugal: results from the 2005/2006 National Health Survey.

BACKGROUND: Understanding the patterns of cervical cytology use in preventive care may provide useful information for an efficient transition from opportunistic screening to organized programmes. We aimed to identify the determinants of non-use and underuse of cervical cytology in Portuguese women. METHODS: As part of the fourth National Health Survey (2005/2006), 2191 women aged between 25 and 64 years were evaluated. The previous use of cervical cytology was classified as never or ever, and, among the latter, those having performed the latest cytology testing >5 years before were considered to underuse cervical cytology. We assessed the determinants of non-use and underuse through age- and education-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Overall, 23.5% of women had never used cervical cytology and 10.7% reported underuse. This prevalence increased with age and decreased with education and income. Compared with the national mean, the lowest risk of non-use and underuse was observed in Norte (non-use: OR = 0.31, 95% CI: 0.23-0.42; underuse: OR = 0.60, 95% CI: 0.40-0.91) and the highest in Alentejo (non-use: OR = 2.33, 95% CI: 1.78-3.06; underuse: OR = 2.37, 95% CI: 1.43-3.93). Women without a private health insurance (OR = 2.65, 95% CI: 1.29-5.47), who had no doctor appointments in the preceding 3 months (OR = 2.06, 95% CI: 1.22-3.48) and those who had never performed a mammography (OR = 17.78, 95% CI: 9.09-34.78) were more likely to have never performed a cervical cytology. CONCLUSION: This study shows inequalities in the use of cervical cancer screening in Portugal and provides useful information for a better allocation of resources for cancer screening.

p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy.

OBJECTIVES: To evaluate the CINtec PLUS assay (mtm laboratories), a new immunocytochemical method for the simultaneous detection of p16(INK4a) and Ki-67, in liquid-based cervico-vaginal cytology, investigating the association of the dual staining with HPV infection and genotyping as well as cytological and histological abnormalities. METHODS: 140 women with a cervico-vaginal sample obtained immediately before the colposcopy were enrolled. This cytological sample was used for HPV testing with the Linear Array HPV Genotyping Test, the dual staining with the CINtec PLUS kit and the morphology assessment. RESULTS: Cytology results were 38 NILM, 16 ASC-US, 32L-SIL, 54H-SIL or worse. 113 patients also had a colposcopy-guided biopsy, classified as 14 negative, 35 CIN1, 24 CIN2, 37 CIN3, 3 invasive SCC. A strong association between p16/Ki-67 and HR-HPV infection was found (COR=6.86, 95% CI: 1.84-31.14). Importantly, the association between p16/Ki-67 positivity and HPV16 and/or 18 infection was 2-fold stronger compared to that with the infection by other HR-HPV types (COR=9.92, 95% CI: 2.39-47.77 vs COR=4.20, 95% CI: 0.99-20.87). In addition, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities (p<0.05 in both cases). p16/Ki-67 positivity resulted strongly associated with a CIN2+ diagnosis (COR=10.86 95% CI: 4.16-29.12). CONCLUSIONS: This preliminary study evidenced that p16/Ki-67 immunostaining might have a relevant clinical role, since the dual staining was significantly associated with HR-HPV infection, particularly with HPV 16 and 18, and the increasing grade of the cervical lesions, the positivity for this biomarker being strongly related to the presence of a CIN2+ lesion.

Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers.

OBJECTIVE: To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer. METHODS: Between April 2007 and March 2010, 6113 women diagnosed with cervical cancer were identified. Cervical cytology and histology slides taken within 10 years of diagnosis were identified and where possible reviewed after a nationally agreed protocol. Reviewers were not blinded to the original reading of each sample. Most cytology samples before 2005 were conventional, most after 2007 liquid based. RESULTS: Of 13,745 cytology results from women developing cervical cancer, 55% were reviewed. The review result was identical for 55% of slides. Of 3759 originally normal slides, only 45% were normal on review: 11% were inadequate, 21% low grade (borderline or mild dyskaryosis) and 23% high grade (moderate dyskaryosis or worse). Of tests originally normal taken over 5.5 years before diagnosis, 14% were upgraded to high grade compared with 37% within 3.5 years of diagnosis. Of 5159 histology specimens recorded within 10 years of diagnosis of a cancer, 3895 were reviewed. Overall, 94% of samples reviewed retained the original diagnosis. One per cent (33/3012) of cancers were downgraded and 5% (6/112) of negative samples were upgraded to cancer upon review (four of which were taken within 2 months of diagnosis). In comparison, 15% (14/91) of cervical glandular intraepithelial neoplasia (CGIN) and 12% (38/314) of cervical intraepithelial neoplasia grade 3 (CIN3) were upgraded to cancer. CONCLUSIONS: In spite of the excellent quality of cytology in England, a high proportion of negative cytology taken up to three and a half years before diagnosis were considered to contain abnormal cells by reviewers informed of the subsequent cancer. Continuing these reviews, with a strong focus on education, will ensure a clear understanding of these slides and further reduce the risk of developing cervical cancer.

Review of negative and low-grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia.

OBJECTIVE: The purpose of the study was to perform a national review of negative, low-grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. METHODS: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high-grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low-grade, atypical or inadequate smear 1-40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. RESULTS: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty-one of 37 women also had high-grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high-grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno- and adenosquamous carcinomas (5/24, P < 0.05). CONCLUSION: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under-diagnosed smears were not related to cancer stage or last cytology report before diagnosis.