hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy.

BACKGROUND: The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+). methods: The study enrolled 1029 women with abnormal screening cytology (years 2006-2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006-2011). RESULTS: During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1-3.1) and 41.8% (95% CI 31.8-53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5-755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation. CONCLUSION: Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.

The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600).

BACKGROUND: In Italy, cervical cancer screening programmes actively invite women aged 25-64 years. Programmes are hindered by low participation. METHODS: A sample of non-responder women aged 35-64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home. RESULTS: Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24-2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61-1.50), a prevalently rural area. CONCLUSIONS: Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.

Immunochemical faecal occult blood test: number of samples and positivity cutoff. What is the best strategy for colorectal cancer screening?

Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml(-1)) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml(-1) as the reference strategy. A total of 20 596 subjects aged 50-69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8 per thousand, and ranged between 2.1 and 3.4 per thousand in other strategies; reference strategy detected 15.6 per thousand advanced adenomas (range=10.0-22.5 per thousand). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5-1.7) for the most specific strategies, whereas it was 2.4-2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources.

Gastric cancer after positive screening faecal occult blood testing and negative assessment.

BACKGROUND: Gastric cancer may be suspected with otherwise unexplained positive faecal occult blood testing. AIMS: To assess the frequency of gastric cancer following positive faecal occult blood testing and negative colonoscopy. SUBJECTS: Age 40-74 cohort at first screening (1985-2001) with (a) faecal occult blood testing- (83,489), (b) faecal occult blood testing +/colonoscopy+ (2025), or faecal occult blood testing+/colonoscopy- (3555). METHODS: Gastric cancer incidence in faecal occult blood testing subsets, compared with expected standardized incidence rates. RESULTS: Gastric cancer risk was increased (standardized incidence rate=146.7; 95% confidence interval: 105.8-203.4) in faecal occult blood testing+/colonoscopy- subjects. A four-fold excess incidence occurred during first year (observed cases=10, standardized incidence rate=408.3; 95% confidence interval: 219.7-758.8), irrespective of faecal occult blood testing type (guaiac, immunological). No excess risk occurred in faecal occult blood testing- (observed cases=53, standardized incidence rate=91.2; 95% confidence interval: 84.1-98.8) or in faecal occult blood testing+/colonoscopy+ subjects (observed cases=2, standardized incidence rate=101.9; 95% confidence interval: 25.5-407.4). Assuming a 100% 3-year study sensitivity for gastric cancer, faecal occult blood testing positive predictive value would be 0.4% (40-74 years) or 0.7% (> or =60 years) in faecal occult blood testing+/colonoscopy- subjects. CONCLUSIONS: Data suggest an association of faecal occult blood testing+/colonoscopy- and excess gastric cancer incidence in the following year. Due to low faecal occult blood testing+ positive predictive value, routine upper digestive tract endoscopy in these subjects is questionable.

Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results.

Screening with faecal occult blood test (FOBT) has been shown to be effective in reducing mortality from colorectal cancer. Tuscany was the first region in Italy in which a screening programme for colorectal cancer by FOBT was initiated region-wide. The aim of the paper was to describe organizational aspects, a quality control model and the results of this experience. From June 2000 to December 2001, 192583 subjects aged 50-70 were invited to undergo a 1-day immunochemical test without any dietary restriction. A total of 78505 subjects (41%) performed the screening test, of whom 4537 responders had a positive test result (5.8%). Among them, 1122 refused any form of assessment or underwent a colonoscopy outside the screening referral centres, with an overall assessment compliance of 75.3%. Malignancies were found in 193 patients and at least a high-risk adenomatous polyp in 692 patients. In about a quarter of the positive subjects who underwent assessment, cancer or high-risk adenoma was detected. In conclusion, data from this experience supported the feasibility of biennial colorectal screening programme by FOBT, particularly regarding invitation compliance and positivity rate. Further efforts are necessary to implement screening extension and to improve data collection.

[Hysteroscopic evaluation of the endometrium in 63 postmenopausal patients treated with tamoxifen for breast cancer]. / Valutazione isteroscopica dell'endometrio in 63 pazienti in post-menopausa trattate con tamoxifene per carcinoma della mammella.

This retrospective analysis intends to evaluate by histeroscopy the endometrial findings in a group of 63 patients in post-menopausal treated with tamoxifen for breast cancer. Our patients assumed tamoxifen for a different period between 6 and 120 months. Patients have been divided in two groups: I) patients undergoing hysteroscopy because of some clinical symptoms; II) patients who undergoing hysteroscopy as a routine examination. The most important observation of this work is the correlation between the presence of negative endometrium and low risk hyperplasia (LRH) associated to: symptomatology and duration of therapy. In the group of asymptomatic patients the LRH is found only after 3 years of treatment, while in the group of symptomatic patients, LRH is present within the first two years of treatment; beyond this period high risk hyperplasia (HRH) and endometrial carcinoma have been diagnosed. We also observed a higher incidence of endometrial polyps in this population than among the non treated group and among the symptomatic patients. From these data we conclude that hysteroscopy follow-up has to be performed in the group of patients treated with tamoxifen and that it would be necessary to have a hysteroscopy before the beginning of therapy and that this one has to be repeated once a year through the treatment. Obviously the symptomatic patients have to undergo hysteroscopy as soon as possible as a higher incidence of HRH and endometrial carcinoma has been detected in this group of patients.

Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening programme.

We evaluated the sensitivity for colorectal cancer (CRC) of the latex agglutination test (LAT), an immunochemical test routinely used in the Florence District screening programme since 2000. Sensitivity was calculated by the proportional interval cancer incidence method in a population of 27,503 consecutive subjects screened in 2000-2002, interval cancers being identified by linkage to the Tuscany Cancer Registry files. Sensitivity was calculated overall and by gender, age, time since last negative LAT, CRC site, and rank of screening. Overall 1- and 2-year sensitivity estimates were 80.7 and 71.5%, respectively, suggesting that faecal occult blood testing screening sensitivity may be suboptimal due to testing or programme quality problems. Increasing screening sensitivity might be achieved if the detection rate of advanced adenomas could be increased without unacceptable loss in specificity.

Lower protection of cytological screening for adenocarcinomas and shorter protection for younger women: the results of a case-control study in Florence.

The efficacy of cytological screening in preventing adenocarcinoma of cervix uteri as compared to squamous cell cancer has been evaluated by means of a case-control study in the province of Florence. The odds ratios of women who had a Pap test within the 3 years before the index date was 0.65 (95% confidence interval (CI) 0.26-1.64) and 0.15 (95% CI 0.07-0.31), for adenocarcinoma and squamous cancer, respectively. The duration of the protective effect was shorter in women below the age of 40 years than in older women.

Vertical transmission of HCV.

BACKGROUND: Knowledge about vertical transmission of HCV is still limited. In this study we followed up the virological status of a series of offspring born to anti-HCV positive, anti-HIV negative mothers. METHODS: Between January 1993 and January 1995, 5000 consecutive, anti-HIV negative pregnant women were screened for anti-HCV (ELISA III) and all positive samples were confirmed by RIBA III and analyzed for HCV-RNA by polymerase chain reaction (PCR). Babies born to anti-HCV positive mothers were followed from birth to two years by testing for ALT levels, anti-HCV antibodies and HCV-RNA. RESULTS: Of 5000 mothers 80 (1.6%) were anti-HCV positive (ELISA III) and RIBA III positive. Of these, 56 (70%) were HCV-RNA positive. We examined 80 babies, born to anti-HCV positive mothers: 56 with HCV-RNA positive mothers and 24 with HCV-RNA negative mothers. Two babies (3.6%) of 56 were anti-HCV and HCV-RNA positive, with normal liver function tests. Seventy-eight babies (97.5%) of 80 (54 with HCV-RNA positive mothers and 24 with HCV-RNA negative mothers) were HCV-RNA negative, with normal liver function tests and detectable levels of anti-HCV antibodies that gradually disappeared between 8-12 months. CONCLUSION: Mother-to-infant transmission of HCV is possible only in the case of HCV-RNA positive mothers. In our study the rate of transmission is 3.6%, (2/56 babies with HCV-RNA positive mothers). HCV transmission may occur without evident association with breast-feeding or vaginal delivery.