Background In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening NTCC study), we compared screening with ...conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year. Methods In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater. For the main endpoint of the study, histologic detection of cervical intraepithelial neoplasia of grade 2 or more (CIN2+), we calculated and compared sensitivity and positive predictive value (PPV) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided. Results For women aged 35–60 years, the relative sensitivity of HPV testing for detection of CIN2+ at a cutoff of 1 pg/mL vs conventional cytology was 1.92 (95% CI = 1.28 to 2.87) and the relative PPV was 0.80 (95% CI = 0.55 to 1.18). At a cutoff of 2 pg/mL HPV DNA, the relative sensitivity was 1.81 (95% CI = 1.20 to 2.72) and the relative PPV was 0.99 (95% CI = 0.67 to 1.46). In this age group, there was no evidence of heterogeneity between study phases. Among women aged 25–34 years, the relative sensitivity for detection of CIN2+ of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 (95% CI = 2.11 to 5.82), statistically significantly larger (P = .019) than that observed in phase 1 at this age (1.58; 95% CI = 1.03 to 2.44). Conclusions For women aged 35–60 years, HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV. Among women aged 25–34 years, the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2+ that are detected by direct referral of younger HPV-positive women to colposcopy. Thus, triage test or repeat testing is needed if HPV is to be used for primary testing in this context.
We collected data from organised Italian cervical screening programmes on (a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) ...the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 25,932 reported colposcopies 38.1% were classified as normal and 20.2% as unsatisfactory. CIN2 or more severe histology was detected in 64.0% of colposcopies classified as grade 2 or higher. Of all colposcopies, the outcome of which was CIN2 or more severe histology, 41.7% were classified as grade 2 or higher. Of the 4,923 women with CIN1, 78.1% had follow-up only. However 0.8% of them had cold-knife conisation, 4.7% were treated by diathermocoagulation and 0.1% had a hysterectomy. Of the 3,788 women with CIN2 or CIN3, 3.9% had not yet been treated when data were collected and no data were available for a further 9.9%. Excision by radio-frequency device was the most common treatment among these women (66.7% of those with known treatment). However 0.7% of all CIN2 and 4.0% of all CIN3 had a hysterectomy. Among the 163 women with invasive carcinoma, 17.2% plausibly with microinvasive disease had only excisional treatment reported.
Data were collected from organised Italian cervical screening programmes on: a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and ...(b) the treatment/management of screen-detected histologically-confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 26,320 reported colposcopies, 39.6% were classified as normal and 11.2% as unsatisfactory. CIN2 or more severe histology was detected in 65.3% of colposcopies classified as grade 2 or higher. Of all colposcopies, the outcome of which was CIN2 or more severe histology, 42.7% were classified as grade 2 or higher. Of the 5,695 women with CIN1, 78.9% were recommended to have follow-up only. However, 1.4% of them had cold-knife conisation and 4.5% were treated by diathermocoagulation. Of the 3,841 women with CIN2 or CIN3, 6.4% had not yet been treated when data were collected, and no data rewere available for a further 12.7%. Excision by radio-frequency device was the most common treatment among these women (64.1% of those with known treatment). However, 0.7% of all CIN2 and 1.7% of all CIN3 had hysterectomy. Among the 151 women with invasive carcinoma, 10.6% plausibly with microinvasive disease, only one treatment LLETZ is reported.
We collected data from organised Italian cervical screening programmes on: a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) ...the treatment/management of screen-detected histologically-confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 30,049 reported colposcopies, 40.3% were classified as normal and 19.9% as unsatisfactory. CIN2 or more severe histology was detected in 66.4% of colposcopies classified as grade 2 or higher. Of all colposcopies, the outcome of which was CIN2 or more severe histology, 41.8% were classified as grade 2 or higher. Of the 5,734 women with CIN1, 73%were recommended to have follow-up only. However, 0.8%of them had cold-knife conisation and 3.8%were treated by diathermocoagulation. Of the 3,713 women with CIN2 or CIN3, 5.1%had not yet been treated when data were collected, and no data were available for a further 15.1%. Excision by radio-frequency device was the most common treatment among these women (68.6% of those with known treatment). However 0.4% of all CIN2 and 3.6% of all CIN3 had hysterectomy. Among the 199 women with invasive carcinoma, 12% plausibly with microinvasive disease had only excisional treatment reported.
We collected, from the local registration systems of Italian organised cervical screening programmes, aggregated data (a) on the correlation between colposcopic grading and histology in routine ...colposcopies and (b) on treatment performed for screen-detected biopsy-proven cervical intraepithelial lesions (CIN). We obtained data on colpo-histological correlation from 40 programmes, reporting on 12,901 colposcopies, classified according to the 1990 international classification. Among them 37% were classified as normal and 25% as unsatisfactory (transformation zone not entirely visible). CIN1 or more severe histology was detected in 2273/4140 (65%) colposcopies classified as grade 1. CIN2 or more severe histology was detected in 566/853 (66.4%) colposcopies classified as grade 2. Of all women with CIN2 or more severe histology 42% had a colposcopy classified as grade 2 or higher. We obtained data on treatment from 57 programmes. Of the 2123 CIN1 cases 63% had follow-up only. However 20 (0.9%) had cold-knife conisation, 2 (0.1%) had hysterectomy and 191 (9.0%) were treated by diathermo-coagulation. Of the 1600 women with diagnosis of CIN2 or CIN3 4.2% had not been treated when data were collected and no data were available for another 8.2%. Electrosurgical excision was the most common treatment in these women (79% of those with known treatment). Some 0.7% of all CIN2 and 5.1% of all CIN3 had hysterectomy. Some 12% of the 111 invasive carcinoma, plausibly microinvasive, had excisional treatment only.
We collected from Italian organised cervical screening programmes data on the correlation between colposcopic findings (according to the 1990 international classification) and histology and on the ...treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were provided as aggregated tables. We obtained data on colpo-histological correlation from 72 programmes. Of the 18,340 reported colposcopies 37.9% were classified as normal and 20.9% as unsatisfactory. CIN2 or more severe histology was detected in 71.6% of colposcopies classified as grade 2 or higher. Of all colposcopies the outcome of which was CIN2 or more severe histology, 40.6% had a colposcopy classified as grade 2 or higher. We obtained data on treatment from 83 programmes. Of the 3,405 women with CIN1 69.3% had follow-up only. However 0.8% of them had cold-knife conisation, 7.5% were treated by diathermocoagulation and 0.1% had hysterectomy. Of the 2,597 women with CIN2 or CIN3 4.1% had not yet been treated when data were collected and no data were available for a further 8.1%. Excision by radio-frequency device was the most common treatment among these women (60.9% of those with known treatment). However 0.7% of all CIN2 and 3.4% of all CIN3 had hysterectomy. Among the 100 women with invasive carcinoma, 17% (plausibly with microinvasive disease) had only excisional treatment reported.
We collected from Italian organised cervical screening programmes data (a) on the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) ...on the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes was provided as aggregated tables. We obtained data on colpo-histological correlation from 63 programmes. Of the 14,745 reported colposcopies 38.9% were classified as normal and 19.6% as unsatisfactory. CIN1 or more severe histology was detected in 2,664/4,877 (54.6%) colposcopies classified as grade 1. CIN2 or more severe histology was detected in 865/1,239 (69.8%) colposcopies classified as grade 2 or higher. Of all colposcopies during which a CIN2 or more severe histology was detected, 40.3% had a colposcopy classified as grade 2 or higher. We obtained data on treatment from 82 programmes. Of the 2,903 women with CIN1, 69.8% had follow-up only. However 25 (0.9%) of them had cold-knife conisation, 212 (7.3%) were treated by diathermocoagulation and 17 (0.6%) had hysterectomy. Of the 2,568 women with CIN2 or CIN3, 4.9% had not yet been treated when data was collected and no data was available for a further 7.5%. Excision by radio-frequency device was the most common treatment among these women (60. 6% of those with known treatment). However, 1.5 % of all CIN2 and 5.5 % of all CIN3 had hysterectomy. Among the 140 women with invasive carcinoma 17.8%, plausibly with microinvasive disease, had excisional treatment only reported.
We collected from Italian organised cervical screening programmes data (a) on the correlation between colposcopic findings (according to the 1990 international classification) and histology and (b) ...on the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely recorded by organised programmes was provided as aggregated tables. We obtained data on colpo-histological correlation from 41 programmes. Of the 16,292 reported colposcopies, 43% were classified as normal and 23 % as unsatisfactory. CINI or more severe histology was detected in 2278/4449 (51%) of colposcopies classified as grade 1. CIN2 or more severe histology was detected in 651/1033 (63%) ofcolposcopies classified as grade 2 or higher. Ofall colposcopies that found CIN2 or more severe histology, 41% had a colposcopy classified as grade 2 or higher. We obtained data on treatment from 71 programmes. Of the 2,895 women with CINI, 73.4% had follow-up only, 14 (0.5%) of them had cold-knife conisation, 170 (5.9%) were treated by diathermocoagulation and 4 (0.1%) had hysterectomy. Of the 1972 women with CIN2 or CIN3, 4.8% had not yet been treated when data were collected and no data was available for a further 12.9%. Excision by radio-frequency device was the most common treatment among these women (58.7% of those with known treatment). However, 0.8% of women with CIN2 and 4.2% of women with CIN3 had hysterectomy. Of the 76 women with invasive carcinoma, 19.8%, plausibly with microinvasive disease, had excisional treatment only reported.
PI3K/AKT/mTOR pathway alterations are frequent in patients with infiltrating breast cancer (IBC). Their clinical and pathological relevance has been insufficiently documented. We evaluated
PI3KCA
for ...mutations and the expression of PTEN, AKT, mTOR and p70S6K by immunohistochemistry in 246 IBC patients treated with hormone therapy (median follow-up, 97 months). A
PI3KCA
mutation was observed in 50 out of 229 informative cases (21.8 %), PTEN loss in 107 out of 210 (51 %), moderate/high level of expression of AKT in 133 out of 188 (71 %), moderate/high level of expression of mTOR in 173 out of 218 (79 %) and moderate/high level of expression of p70S6K in 111 out of 192 cases (58 %).
PI3KCA
mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling. The expression of p70S6K was associated with a high level of mTOR immunoreactivity, and high PTEN expression was associated with high AKT expression level. Univariate analysis showed that
PI3KCA
mutation status was not associated with clinical outcome in the series as a whole or in the node-negative subgroup. However, in the node-positive subgroup, exon 9
PI3KCA
mutation was associated with unfavourable overall survival (OS), although its impact on the final model in multivariate analysis seemed to be limited. Of the other markers, only high p70S6K expression was associated with a significantly prolonged OS.
PI3KCA
mutation status is of limited prognostic relevance in oestrogen receptor-positive breast cancer patients treated with hormone therapy.
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