"Low-grade positivity" of HPV viral load after atypical squamous cells of undetermined significance (ASC-US) cytology identifies women at low-risk for cervical intraepithelial neoplasia grade 2 and 3.

The correlation between high-risk HPV-DNA viral load, expressed as relative light units (RLU) values obtained from the Hybrid Capture 2 (HC2) test, and the prevalence of CIN2/CIN3 was investigated and statistically analyzed in 614 ASC-US consecutive cases. Cases were categorized into three groups according to RLU values: "low-grade positivity", "intermediate positivity" and "high-grade positivity", and the prevalence of CIN2/CIN3 was evaluated in the single groups and compared among them. CIN/CIN3 rates demonstrated a significant (p < 0.001) increase with a direct correlation with increasing RLU values: 4.6% (RLU from 1.0 to 10.0), 9.1% (RLU from 11.0 to 100.0) and 32.2% (RLU > 100.0) respectively. The prevalence of CIN2/CIN3 between the group with RLU < 10.0 (4.6%) and the group with RLU > 10 (24.2%) showed statistical significance (p = 0.0002). Increasing hrHPV viral load significantly correlates with increasing prevalence of CIN2/CIN3 in ASC-US cases.

Human papillomavirus viral load expressed as relative light units (RLU) correlates with the presence and grade of preneoplastic lesions of the uterine cervix in atypical squamous cells of undetermined significance (ASCUS) cytology.

Human papillomavirus (HPV) testing is more sensitive and has higher negative predictive value (NPV) than the Pap test for the detection of cervical intraepithelial neoplasia (CIN) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology, but has low specificity, leading to high referral rates to second-level triage. Our goal was to identify the prognostic significance of HPV viral load figures. We evaluated whether a correlation between viral load, expressed as relative light units/cutoff (RLU/CO), and the severity of cervical lesions existed in 614 ASCUS cases. Hybrid Capture 2 (HC2®) RLU/CO values, categorised into five classes, were correlated to clinical outcomes and statistically analysed. A significant correlation (p < 0.0001) was observed between increasing RLU values and the prevalence of high-grade CIN (CIN2/CIN3). The mean RLU values for negative, low-grade and high-grade lesions were 68.1, 172.5 and 1,020.0 RLU/CO, respectively (p < 0.0001). CIN2/CIN3 ranged from 4% for 0 < RLU/CO values ≤ 1, to 5% for 1 < RLU/CO values ≤ 10, to 9% for 10 < RLU/CO values ≤ 100, to 23% for 100 < RLU/CO values ≤ 1,000 and to 48% when RLU/CO values were >1,000 (p < 0.05). The HPV viral load in ASCUS cases significantly correlates with the severity of cervical cancer precursors. These data may have prognostic value, as they significantly correlate with the probability of a CIN2+ .

A limited autoimmunity to p185neu elicited by DNA and allogeneic cell vaccine hampers the progression of preneoplastic lesions in HER-2/NEU transgenic mice.

Prevention of the progression of precancerous lesions by vaccines is virtually uncharted territory. Their potential, however, is being assessed in transgenic mice which develop autochthonous tumors with defined stages of progression. In this paper we show that the DNA micro-array technology significantly helps assessment of the preventive efficacy of a combined DNA and cell vaccine. All female rat Her-2/neu transgenic BALB/c (BALB-neuT) mice develop an invasive carcinoma in each of their mammary glands within 25 weeks of age. This is elicited by the activated transforming rat Her-2/neu oncogene embedded in their genome. We have previously shown that vaccination of mice bearing multiple in situ carcinomas with DNA plasmids which code for the extracellular and transmembrane domain of rat p185neu, the product of the rat Her-2/neu oncogene, followed by a boost with rat p185neu+ allogeneic cells engineered to secrete interferon-gamma, keeps 48% of mice tumor free until week 32. We have now extended our follow-up until mice reach one year of age and show that protection vanishes as time progresses. This observation suggests that the accuracy of the results studying immunotherapy against life-threatening tumors is a function of the length of the follow-up. The application of microarrays, and the concordance of morphologic and gene expression data led us to identify antibody as the main mechanism induced by vaccination. Protection is associated with a break of tolerance and a limited autoimmunity against the endogenous mouse p185neu.