Interobserver reproducibility of cytologic p16INK4a /Ki-67 dual immunostaining in human papillomavirus-positive women.

BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists. RESULTS: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643]). CONCLUSIONS: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society.

In a cohort of breast cancer screened patients the proportion of HER2 positive cases is lower than that earlier reported and pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases.

Human epithelial growth factor receptor 2 (HER2) overexpression and/or amplification is of predictive and prognostic value in infiltrating breast carcinoma (IBC). We evaluated the proportion of HER2-positive cases (score 3 overexpression/score 2 plus fluorescence in situ hybridization (FISH) amplification) in a consecutive series of 2163 patients. According to immunohistochemical analysis of HER2 expression, using Herceptest and FDA criteria, 839 cases had score 0, 476 score 1+, 699 score 2+, and 149 score 3+. Of the 699 scoring 2+ cases, 160 (22.88 %) showed Her2 gene amplification by FISH analysis, making a total of 309 (14.28 %) HER2-positive cases. Grade 1 ductal and special type IBC were never HER2 positive, while only three infiltrating lobular carcinomas but a relevant percentage of small IBC were HER2 positive. Of HER2-positive cases, 52.1 % was pT1 and of these, 38.5 % was pT1b or smaller. Logistic regression analysis revealed that estrogen receptor (ER), progesterone receptor (PgR), grade, and pT were significantly associated with HER2 positivity and that HER2 3+ cases were more frequently of higher grade and pT than HER2 2+/Her2 amplified cases. In addition, HER2 3+ cases were more frequently in ER and PgR negative than HER2 2+/Her2 amplified cases. We conclude that the proportion of HER2 positive cases is lower than that reported in older literature and that pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases.

Incidence and mortality data from cutaneous melanoma in Trentino: registry-based study.

BACKGROUND: The province of Trento has been the target of health campaigns for early diagnosis of cutaneous melanoma for 30 years. OBJECTIVE: To evaluate incidence and mortality data of skin melanoma in the province from January 1992 to December 2001. METHODS: The study is based on the provincial skin cancer registry and the regional mortality registry. Standardized incidence and mortality rates were computed, and time trends were evaluated. Incidence rates were modeled using Poisson regression. RESULTS: Five hundred fifty-four melanomas were diagnosed (226 in males and 328 in females). No period effect was revealed. Incidence rates in females were about 1.24 times those in males. No significant trend in mortality rates was observed. CONCLUSION: We examined incidence and mortality data of cutaneous melanoma during a 10-year period and failed to find any significant trend. It seems we have reached a plateau after many years of continuous, intensive health campaigns.

The cytological screening turned out effective also for adenocarcinoma: a population-based case-control study in Trento, Italy.

To evaluate the effectiveness of a cytological screening to prevent invasive cervical cancer in the province of Trento, a northern Italian area where a population-based cancer registry is active. The history of Pap test was evaluated through a case-control study in 61 population-based invasive cervical cancer patients, incident during 1995-2000, and in 244 age-matched (between 25 and 75 years old) controls. Women who had at least one Pap test had a reduced risk of invasive carcinoma of 80% (odds ratio=0.20; 95% confidence intervals 0.10-0.40). The protection of a previous Pap test for both squamous cell carcinoma (odds ratio=0.23; 95% confidence intervals 0.09-0.58) and adenocarcinoma (odds ratio=0.24; 95% confidence intervals 0.07-0.78) was similar. The overall protective effect of the Pap test was not seen among younger women (<40 years). The protective effect of the Pap test seems to be stronger for shorter intervals. Our study confirms that Pap-test screening, particularly in middle-aged and older women, is an effective public health intervention with encouraging results also for the prevention of cervical adenocarcinoma.

HPV triage for low grade (L-SIL) cytology is appropriate for women over 35 in mass cervical cancer screening using liquid based cytology.

In the experimental arm of a randomised trial, women were tested both for liquid-based cytology and human papillomavirus (HPV) DNA and referred for colposcopy if cytology was ASCUS (atypical cells of undetermined significance) or more severe. We considered those with ASCUS (757) or LSIL (low-grade squamous intraepithelial lesions) (485) and a valid HPV test who received colposcopy. We computed sensitivity, specificity and ROC curves with different values of relative light units (RLU, that are related to viral load) as cut off, using cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) at blind histology review as the endpoint. The area under the receiver operating characteristic (ROC) curve was significantly less among women aged 25-34 years than in those older, both considering ASCUS/AGUS (atypical glandular cells of undetermined significance) (p=0.0355) and LSIL (p=0.0009). At age 35-60 the curves for ASCUS and LSIL were similar, while at age 25-34 the area under the curve for LSIL was significantly less than for ASCUS (p=0.0084). With LSIL cytology, specificity of Hybrid Capture 2 with 2 RLU cut-off was 35.0% (95%CI 28.4-42.1) at age 25-34 and 64.5% (95%CI 58.3-70.3) at age 35-60. In conclusion, triaging by HPV testing performed better in women aged over 35 years than those younger. For older women, HPV triaging should also be considered for managing those with LSIL cytology.

Epidemiology of skin tumors: data from the cutaneous cancer registry in Trentino, Italy.

BACKGROUND: A Skin Cancer Registry was established in the province of Trento in northeast Italy in 1992 with the aim of collecting data on all cutaneous tumors affecting residents. These neoplasms are responsible for considerable morbidity and utilization of the Health Service because of their high frequency and, therefore, knowledge of the exact incidence is very important in planning health policies. Registry data are also very helpful in performing studies of analytical and descriptive epidemiology. METHODS: For each patient, we collected personal data, phenotypical characteristics, professional history, concurrent diseases, previous therapy or trauma, and all data regarding the tumors. Patients were interviewed in person or, less frequently, by phone. All data were verified and put in a computerized file, in a protected room. The Statistics Institute of Trento University analyzed the data. Comparison among means was performed using the analysis of variance and differences among proportions were tested by chi-squared analysis. Poisson regression and the likelihood ratio test were used to compare incidence rates. We analyze here the data regarding epiteliomas and melanoma. RESULTS: During the study period we registered 3435 primary skin tumors in 2868 individuals. Crude incidence rates, calculated using the number of subjects (not the number of tumors), were 87.9 for basal cell carcinoma (BCC), 28.9 for squamous cell carcinoma (SCC), and 14.2 for cutaneous melanoma (CM), per 100,000 per annum. We also calculated the same figures in females and males and specific incidence rates in both sexes and evaluated the distribution of skin cancer according to sex and anatomical site. CONCLUSION: We report the analysis of the data collected by the Skin Cancer registry in a 6 year period and compare the data with published data in literature and with data of a previously registered melanoma file. Our results confirm the high incidence of nonmelanoma skin cancers and the variation in the histological patterns of CM.