No abstract

These data indicate that cigarette smoking is not an independent risk factor of CIN2+, but the increased risk ascribed to smoking is mediated by acquisition of HR-HPV, of which current smoking was an independent predictor in multivariate model.

The rates of acquisition and the times of incident high-risk (HR) human papillomavirus (HPV) infectionsand Pap smear abnormalities and their predictive factors were analyzed in women participating in a multicenter screening study in three countries of the New Independent States of the former Soviet Union. The 423 patients were prospectively monitored for a mean of 21.6 months. At the baseline, 118 women were HR HPV DNA negative (Hybrid Capture II assay) and Pap smear negative (group 1), 184 were HPV DNA positive and Pap smear negative (group 2), and 121 were HPV DNA negative and Pap smear positive (group 3). The time to the acquisition of an incident abnormal Pap smear (19.4 months) was significantly longer in group 1 than in group 2 (9.2 months) (P ‫؍‬ 0.0001). The times of acquisition of incident HR HPV infection were 16.6 and 11.0 months in group 1 and group 3, respectively (P ‫؍‬ 0.006). The monthly rates of acquisition of incident HR HPV infections were very similar in group 1 (1.0%) and group 3 (0.8%), whereas the rate of acquisition of an abnormal Pap smear was significantly higher in group 2 (3.1%) than in group 1 (1.5%) (P ‫؍‬ 0.0001). The acquisition of HR HPV infection (but not a positive Pap smear result) was significantly (P ‫؍‬ 0.0001) age dependent. The only significant independent (P ‫؍‬ 0.001) predictor of the incidence of an abnormal Pap smear result was a high HR HPV load of >20 relative light units/control value (CO) (rate ratio, 2.050; 95% confidence interval, 1.343 to 3.129). Independent predictors of incident HR HPV infection were patient category (a sexually transmitted disease) and ever having been pregnant. The time of acquisition of HR HPV infection was 3 months shorter than that of an abnormal Pap smear. At the baseline the high load of a particular HR HPV type is the single most important predictor of an incident Pap smear abnormality, whereas young age and having a sexually transmitted disease predict incident HR HPV infections.The accumulated data from prospective follow-up studies suggest that the natural history of clinical human papillomavirus (HPV) infections of the uterine cervix is basically identical to that of cervical intraepithelial neoplasia (CIN) lesions, with (i) progression, (ii) persistence, and (iii) regression as the main outcome measures (7,13,23). However, special features of the natural history of HPV infections seem to be intimately linked to different risks of the development of cervical cancer (7,22,30,31). These include the presence of latent and subclinical HPV infections and the propensity of the virus to remain persistent (latent) for prolonged periods or to become reactivated or for the infection to undergo spontaneous resolution (3,7,22,30,31).This HPV involvement forms the biological basis of additional patterns recently described in studies of the natural history of CIN lesions, called early regression, fluctuation, and late regression (3,20,21,23,24). It seems obvious that the HPV type, viral load, the acquisition of new (incident) infections, as wel...

The results of this study indicate that women and girls in these NIS countries are conservative in many key characteristics of "high-risk" sexual behavior, such as age at onset of sexual activity, number of partners, and casual sex partners. HPV-positive and HPV-negative groups are clearly distinguished by the same variables identified as the key risk factors of HPV infection and cervical intraepithelial neoplasia in Western countries.

No abstract

The impairment of retinoic acid (RA)-dependent signaling is a frequent event during carcinogenesis. Cellular retinoic acid-binding proteins (CRABP1 and CRABP2) are important modulators of RA activity. Up to date, the role of these proteins in cancer progression remains poorly investigated. Here, we studied for the first time the simultaneous messenger RNA (mRNA) and protein expression of CRABPs in non-small cell lung cancer (NSCLC) samples. CRABP1 and CRABP2 mRNA levels were elevated in 42 and 56 % of NSCLC samples, respectively. Decrease of CRABP2 mRNA expression was significantly associated with the presence of lymph node metastases. Protein expression of CRABP1 and CRABP2 was detected in 50 and 56 % of tumor samples, respectively. We also found a positive correlation between CRABP1 and CRABP2 expression. Taken together, we demonstrated significant changes in CRABP expression in NSCLC samples. Importantly, the presented data provide the first evidence of potential involvement of CRABP2 in lung cancer metastasis.

CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood. Here, for the first time we demonstrated pro-metastatic and pro-tumorigenic activity of CRABP1 in mesenchymal tumors. Further functional analysis revealed that the pro-tumorigenic effect of CRABP1 does not depend on retinoic acid binding activity. These results suggest that CRABP1 could have an alternative intracellular functional activity that contributes to the high malignancy of transformed mesenchymal cells. Microarray analysis detected CRABP1-mediated alterations in the expression of about 100 genes, including those encoding key regulatory proteins. CRABP1 is ubiquitously expressed in monophasic synovial sarcomas, while in biphasic synovial sarcomas it is expressed uniquely by the spindle cells of the aggressive mesenchymal component. High level of CRABP1 expression is associated with lymph node metastasis and poor differentiation/high grade of pancreatic neuroendocrine tumors (pNETs). Presented data suggest CRABP1 as a promising biomarker of pNETs' clinical behavior. Our results give the first evidence of pro-tumorigenic and pro-metastatic activity of CRABP1 in mesenchymal and neuroendocrine tumors.

Data are controversial as to the role of menarche age as a risk factor of high-risk human papillomavirus (HR-HPV) infections. The objective of this study was to analyse the risk estimates for age at menarche as determinant of cervical intraepithelial neoplasia (CIN) and HR-HPV infections. A cohort of 3187 women were stratified into three groups according to their age at menarche: (i) women <13 years of age; (ii) those between 13 and 14 years and (iii) women >15 years of age. These groups were analysed for predictors of (a) HR-HPV, (b) high-grade CIN and (c) outcome of HR-HPV and cytological abnormalities during prospective follow-up. All the three groups had identical prevalence of HR-HPV, Papanicolaou smear abnormalities and CIN grades. In contrast to menarche age itself, the time from menarche to the first intercourse (TMI), to the first pregnancy (TMP) and to the first delivery (TMD) were all significant (P = 0.0001) predictors of HR-HPV (but not CIN2) in univariate analysis, but lost their significance in a multivariate model. Outcome of cervical disease and HR-HPV infection was unrelated to menarche age, the latter and the three intervals being not predictors of CIN2 in a multivariate model. In conclusion, age at menarche and the intervals between menarche and (i) onset of sexual activity, (ii) first pregnancy and iii) first delivery, are not independent predictors of HR-HPV infections and CIN2 in multivariate analysis.