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.

Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for patients with squamous epithelial lesion of the uterine cervix.

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene in association with human papillomavirus (HPV) 16 E6 variants has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. The association of p53 codon 72 polymorphism alone and in combination with specific HPV 16 E6 variants with risk of developing squamous intraepithelial cervical lesion has been investigated in low and high-grade squamous intraepithelial lesions and in HPV-negative controls from an Italian population. The data obtained showed statistically significant different distribution of p53 genotypes between healthy controls and precursor lesions, with the p53 arginine homozygous increased in high-grade squamous intraepithelial lesions. The T350G HPV 16 variant was the most frequent variant observed in the analyzed group of Italian women, showing a slight decreasing with the severity of the lesion. At the same time, the number of the prototype T350 slightly increased with the severity of the cytological lesions. In conclusion, p53 arginine homozygous was found to be increased in high-grade lesions, supporting the results of previous investigations indicating that HPV-positive patients with p53 Arg/Arg have an increased risk of developing pre-cancerous lesions. In addition, T350G HPV 16 variant was over-represented in p53 Arg homozygous women with cervical lesions. When p53 genotype and HPV 16 variants are considered together, no difference emerges between cases and controls so is not possible to assess that the oncogenic effect of HPV 16 T350G variant may be influenced by the p53 genotype.

Comparison of clinical performance of Abbott RealTime High Risk HPV test with that of hybrid capture 2 assay in a screening setting.

Randomized trials have produced sound evidence about the efficacy of screening with human papillomavirus (HPV) DNA tests in reducing cervical cancer incidence and mortality. We evaluated the clinical performance and reproducibility of the Abbott RealTime High Risk (HR) HPV test compared with that of the HR hybrid capture 2 (HC2) assay as assessed by a noninferiority score test. A random sample of 998 cervical specimens (914 specimens of cervical intraepithelial neoplasia less severe than grade 2 [

Hybrid capture 2 and cobas® 4800: Comparison of performance of two clinically validated tests for human papillomavirus primary screening of cervical cancer.

OBJECTIVE: To compare, in a primary human papillomavirus screening setting, two different validated human papillomavirus tests, considering their analytical and clinical screening performances. METHODS: In Tuscany, a human papillomavirus screening program was implemented in 2013. Hybrid capture 2 (Qiagen) was used for testing until May 2016, when it was replaced by the cobas® 4800 human papillomavirus test (Cobas; Roche). We evaluated the performance of Hybrid capture 2 and Cobas on: the same screening population in two different periods (before and after changing to Cobas); the same Hybrid capture 2-positive consecutive samples. Discordant samples (Hybrid capture 2-positive/Cobas negative) were typed on the L1 gene (reverse line blot, AB Analitica) and E6/E7 genes (BD Onclarity assay). RESULTS: In the considered time period (n = 37,775), human papillomavirus positivity was 9.8% and 7.4%, respectively, for Hybrid capture 2 and Cobas (p < 0.0001). At immediate colposcopy, the cervical intraepithelial neoplasia, grade 2 positive predictive value was, respectively, 23.8% and 34% (p < 0.001). At one-year recall, human papillomavirus persistence was, respectively, 40.6% and 62.2% (p < 0.0001). Of Hybrid capture 2-positive re-tested samples (n = 620), 32.4% were Cobas negative. Of discordant samples typed on L1, 7% were positive for the 12 high-risk human papillomavirus. Of the samples found to be negative for the 12 high-risk human papillomavirus types on L1, 14.5% were positive on E6/E7 typing. Among the discordant samples, the only two cervical intraepithelial neoplasia (CIN) grade 3 lesions were non-high-risk human papillomavirus positive on both L1 and E6/E7 typing. CONCLUSION: At baseline, Hybrid capture 2 showed greater human papillomavirus positivity and a lower CIN2+ positive predictive value than Cobas, which was more specific than Hybrid capture 2 in detection of high-risk human papillomavirus: 80% of discordant samples were confirmed as high-risk human papillomavirus negative. This higher analytical specificity determined the non-identification of two CIN3 lesions.

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

Rheumatoid arthritis: follow-up and response to treatment.

OBJECTIVE: To assess the role of diagnostic imaging techniques in the identification and follow-up of the anatomical damage induced by the chronic inflammatory process of rheumatoid arthritis (RA) not only to study the natural history of the disease but also and especially to assess the long-term response to disease-modifying anti-rheumatic drugs (DMARD). MATERIALS AND METHODS: The relative literature data were reviewed and compared with our personal experience with different imaging modalities such as conventional radiography (CR), ultrasound (US) and magnetic resonance imaging (MRI). RESULTS: Several radiologic techniques have been used over the years to study articular damage in RA: they describe and quantify the articular damage (semi-quantitative analysis) based on a series of parameters and elementary anatomical lesions which are given a rising score. For its sensitivity in detecting early disease signs and the possibility to express anatomical damage progression quantitatively, Sharp's index is considered the best tool for evaluating RA patients. The close correlation between clinical parameters and the radiologic scores obtained regardless of the method applied led to a new concept of anatomical damage related to the 'radiologic progression of the disease' which is a more precise measure of RA severity than the single isolated radiograph. The progression of radiologic damage in rheumatoid arthritis is expressed as the number or proportion of new eroded joints/year: independent of the index adopted and the terms used to express progression, severe radiologic damage occurs in the early disease stage, involving approximately 2% of the joints within about 1 year, and 13% within 2 years, with an estimated average annual progression of 1.3%. Radiologic techniques evaluate the anatomical damage in the course of RA only with reference to the osseous component of the joint and therefore apply to a disease stage that is largely irreversible. MRI and US detect the soft-tissue damage occurring in the earlier phases and are more likely to respond to early treatment. The former technique appears to be useful to detect soft-tissue damage like synovial pannus, intra- and periarticular and peritendinous effusion, capsuloligamentous articular and tendon changes. Its high sensitivity for minimal bone erosions and chondromalacia has been demonstrated. US allows to demonstrate a wide range of soft-tissue changes of the hand and wrist. Joint-cavity widening, loss of cartilage definition, bone erosions, widening of flexor tendon sheath and tendon structure are also well depicted on ultrasound images. CONCLUSIONS: CR is the central tool in the diagnosis, staging and follow-up of RA patients and in general in the assessment of treatment efficacy; MRI and US are complementary tools.

Effectiveness of a home-based strengthening program for elderly males in Italy. A preliminary study.

BACKGROUND AND AIMS: The practice of regular physical exercise has been shown to be effective in slowing the age-related progressive functional deterioration. Most exercise trials have been conducted with supervised training programs. The purpose of this study was to investigate the effectiveness of a 4-month home-based strength training on strength, function and personal satisfaction. METHODS: Ten elderly men (mean age 68.5 years) were enrolled for home-based training one month after completing a 4-month supervised program; 12 age-matched men served as the control group. Subjects were asked to perform 3 sessions a week consisting of six resistance exercises with elastic bands involving the major muscle groups of the upper and lower limbs. We had calculated the correlation between the elongation and resistance of the elastic bands. The subjects were instructed to keep a diary reporting the execution of the session. We measured dynamic concentric strength of the muscle groups involved in the resistance exercises and maximal isometric strength of the knee extensors and elbow flexors before and after the 4-month home training. The Satisfaction Profile (SAT-P) questionnaire was administered before and one month after the completion of the training program for assessing personal satisfaction. RESULTS: The final to baseline comparison showed a non-significant decrease in mean isometric maximal strength values for knee extensors and elbow flexors in the control group, while the exercise group significantly (p=0.001) improved the average baseline values. Maximal dynamic concentric strength values decreased significantly in the control group, while significant improvements were observed in the exercising subjects. The SAT-P questionnaire did not show any difference in either group from baseline. The adherence-to-protocol rate based on self-report was 78%. CONCLUSIONS: Home training with elastic bands appears to be an effective low-cost modality of maintaining strength and function in an elderly population.