Endocervicoscopy and Biopsy to Detect Cervical Intraepithelial Squamous Neoplasia in Nonvisible Squamocolumnar Junction With Unsatisfactory Colposcopy: A Pilot Study.

The aim of this study was to investigate the practical utility of endocervicoscopy and targeted biopsy in high-risk human papilloma virus-positive women with abnormal squamous cells on cervical cytology and unsatisfactory colposcopy with nonvisible squamocolumnar junction. Seventy-seven high-risk human papilloma virus-positive patients with abnormal cervical cytology for squamous cells bearing type 3 transformation zone were enrolled. Endoscopic examination of the endocervical epithelium, with office-based continuous-flow hysteroscopy after application of acetic acid 5%, followed by targeted biopsies and consequent large loop excision of the transformation zone was carried out. Sensitivity, specificity, positive predictive value and negative predictive value of endocervicoscopy, and orientated biopsy were confronted with the results of large loop excision of the transformation zone (referral test). The sensitivity and specificity of endocervicoscopy and orientated biopsy for low-grade cervical intraepithelial neoplasia were 53% and 81%, respectively, while the sensitivity and specificity for high-grade cervical intraepithelial neoplasia were 64% and 47%, respectively. The positive predictive value for low-grade cervical intraepithelial neoplasia was 64% and for high-grade cervical intraepithelial neoplasia was 88%. The negative predictive value for low-grade cervical intraepithelial neoplasia was 87% and for high-grade cervical intraepithelial neoplasia was 41%. Endocervicoscopy is a safe, office-based technique. It is a reliable method to detect the transformation zone in patients with type 3 transformation zone and unsatisfactory colposcopy. It potentially allows target biopsy of the transformation zone but presents a relatively low specificity/negative predictive value to predict high-grade cervical intraepithelial neoplasia, thus negative biopsy results should be interpreted with caution.

Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

BACKGROUND: Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl ß-glucan (Colpofix®) gel as adjuvant therapy in HPV infection. METHODS: The medical records of patients attending the Colposcopy Service of four hospitals in Rome from 2011 to 2013 were collected. Case arm consisted of patients submitted to local therapy with Colpofix®. Control arm comprised patients who did not receive this therapy. A total of 999 patients were included, divided into four groups, according to their cytological and histological specimens, colposcopy and subsequent management. RESULTS: Local therapy with Colpofix® gel resulted effective with respect to no therapy for the regression of low-grade CIN (CIN1) in patients submitted to follow up (P=0.0204), while it was no effective for the regression of CIN1 submitted to ablative therapy and high-grade CIN (CIN 2+) (P value not significant). CONCLUSIONS: In conclusion, Colpofix® gel represents a valid alternative to "wait and see" strategy in patients affected by CIN1. Further prospective studies are warranted to confirm these results.

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

BACKGROUND: The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. OBJECTIVE: The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. STUDY DESIGN: Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. RESULTS: The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. CONCLUSION: HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up.

Multiple intraepithelial neoplasias of the lower female genital tract: the reliability of HPV mRNA test.

OBJECTIVE: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms. MATERIALS AND METHODS: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment. RESULTS: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02). CONCLUSIONS: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia.

OBJECTIVE: To determine pregnancy outcomes among women who underwent loop electrosurgical excision procedure (LEEP). METHODS: In a case-control study in Italy, 475 pregnant women who underwent LEEP and 441 untreated pregnant women were enrolled between January 2003 and January 2007. Outcome measures were spontaneous abortion, preterm delivery, and at-term delivery rates. Continuous and discrete variables were analyzed via t, χ(2), and Fisher exact tests. Groups were compared by analysis of variance and Tukey HSD test. RESULTS: The spontaneous abortion rate was 14.5% and 14.1% in the LEEP and untreated groups, respectively. The preterm delivery rate was 6.4% and 5.0% in the LEEP and untreated groups, respectively. The number of women with a cervical length of less than 30mm was higher in the LEEP group, but this did not influence preterm delivery rate (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.53-1.95). Among women with a cervical length of less than 15mm, those treated with a wider removal of cervical tissue showed increased risk of preterm delivery (OR, 5.31; 95% CI, 1.01-28.07). CONCLUSION: The preterm delivery rate was not higher among women who underwent LEEP than among untreated women. Preterm delivery was associated with cone size and cervical length in the second trimester.

Comparison of conventional Papanicolaou smears and fluid-based, thin-layer cytology with colposcopic biopsy control in central Italy: a consecutive sampling study of 461 cases.

The aim of this study was to compare the cytologic diagnosis and specimen adequacy of conventional Papanicolaou (CP) and fluid-based, thin-layer [ThinPrep (TP), Cytyc, Boxborough, MA] cervical cytology in a population from central Italy. CP and TP samples were collected simultaneously using a consecutive sampling method on women presenting for cervical screening. Colposcopy was performed as clinically indicated, and biopsy results were compared with cytologic diagnoses. Among the 461 patients included in the study, 413 were negative at both CP and TP, 9 had unsatisfactory results at both tests and 39 patients presented abnormal results at CP, TP or both. Cohen's Kappa was 0.77 showing good agreement between CP and TP test results. Histological data were available for 20 (51.28%) of the 39 patients with at least one positive test. Among the 13 patients with HSIL at histology, 7 had HSIL at CP (sensitivity 53.85%) and 5 at TP (sensitivity 38.46%). For all three patients with squamous cell carcinoma (SCC) at histology, CP and TP had shown the same diagnosis (sensitivity 100%). The positive predictive values were 33.33% for CP and 25.0% for TP regarding the LSIL diagnosis and 100% for both CP and TP regarding HSIL and SCC diagnoses. Our results may be influenced by the consecutive sampling procedure.

Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in vivo: results from a pilot clinical study.

Raloxifene (RAL), a selective estrogen receptor modulator, is indicated for the prevention and treatment of postmenopausal osteoporosis. RAL, by decreasing bone turnover, prevents bone loss and microarchitecture damage, reducing the incidence of osteoporotic fractures. Our previous in vitro data demonstrated that RAL modulates osteoclast activity by, at least in part, an IL-6- and TNF-alpha-dependent mechanism. In this study we evaluated the effects of RAL treatment (60 mg/d) on circulating levels of these cytokines in 14 postmenopausal women with osteoporosis. Lumbar bone density (determined by dual energy x-ray absorptiometry) and IL-6 and TNF-alpha levels were measured before and after 6 and 24 months of therapy. After 24 months, RAL increased bone density. IL-6 and TNF-alpha expression, elevated before treatment, significantly decreased (50% and 30%, respectively) after 6 months. This effect was sustained up to the end of the treatment (75% and 35%, respectively). Thus, our data show that RAL can modulate circulating levels of cytokines involved in osteoclastogenesis and bone resorption, suggesting that modulation of soluble factors could play a pivotal role in the mechanisms of the osteoprotective effect of RAL.