Prevalence of Multiple High Risk Human Papilloma Virus (HR-HPV) Infections in Cervical Cancer Screening in Lazio Region, Italy.

Background/Aim: It has been well established that human papilloma virus (HPV) is the major cause of cervical pre-cancerous lesions and cervical cancer. Extended HPV genotyping has pointed out that co-infections with multiple high-risk (HR)-HPV genotypes not only is possible and quite frequent, but also has different prognoses. The purpose of this study was to evaluate the prevalence of co-infections in women tested for HR-HPV in the national cervical cancer screening program of Lazio (Italy). Patients and Methods: From June 1st to November 30th 2022, we analyzed 30,445 samples of women aged between 30 and 64 years, using the Anyplex TM II HPV HR Detection test by Seegene (Arrow), which identifies 14 HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68. The data were analyzed using the SG STATS platform. Results: In total, 4,244 (13.94%) were positive: 3,290 (77.52%) showed a single genotype infection and 954 (22.48%) an infection with 2 to 5 different genotypes. In 721 (75.60%) cases, two different genotypes were detected, in 191 (20.00%) there were three genotypes, in 41 (4.30%) cases there were four genotypes and in only one case (0.10%) five different genotypes were detected. HPV 16 (262 cases of co-infections) was associated in 27 cases with HPV 31 genotype, in 25 cases with HPV 68 and in 18 cases with HPV 58. Conclusion: HPV 16 was the most frequent genotype detected in co-infections. Immunity status, vaccination, lifestyle, and other possible risk factors, such as the combination of the HR-HPV genotype multiple infections, may influence the development and progression of the disease.

Detection of 14 High-risk Human Papillomavirus (HPV) Genotypes Within the Italian Cervical Cancer Screening.

BACKGROUND/AIM: The identification of high-risk human papillomavirus (HR HPV) genotypes is important both for epidemiological purposes and because the persistence of an HPV infection with the same genotype is a necessary condition for the development of cervical cancer. The purpose of this study was to analyze the prevalence of HR HPV genotypes in women enrolled in the national program for cervical cancer screening in Lazio Region, Italy. PATIENTS AND METHODS: From April to November 2022, we evaluated 30,445 samples using the Anyplex TM II HPV HR Detection test (Seegene), which identifies 14 HR HPV: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. The data were analyzed using the SG STATS platform. RESULTS: In total, 4,244 samples tested positive (13.9%); 3,290 samples (77.5%) were positive for one of the genotypes tested, and 954 (22.5%) were positive for more than one HPV genotype. The total prevalence (considering both single infection and co-infections) of the different genotypes was: HPV 16 755 cases (13.8%), HPV 31 704 (12.9%), HPV 68 580 (10.6%), HPV 66 436 (8.0%), HPV 52 413 (7.5%), HPV 58 411 (7.5%), HPV 51 400 (7.3%), HPV 56 366 (6.7%), HPV 39 293 (5.3%), HPV 59 260 (4.8%), HPV 45 231 (4.2%), HPV 33 230 (4.2%), HPV 18 222 (4.0%), HPV 35 173 (3.2%). Our results indicate that HPV 16 and 31 are the most prevalent genotypes in the Lazio region followed by HPV 68, 66, 52, 58, and 51. CONCLUSION: The extended genotyping test allows a better risk stratification and the identification of multiple HPV infections.

PRb2/p130, p107 and p53 expression in precancerous lesions and squamous cell carcinoma of the uterine cervix.

The aim of this study was to investigate pRb2/p130, p107 and p53 expressions in precancerous lesions and squamous cell carcinoma (SCC) of the uterine cervix. We evaluated Human Papillomavirus (HPV) testing and typing and pRb2/p130, p107 and p53 expressions (antibody D07) of 48 patients showing low-grade cervical intraepithelial neoplasia (LCIN, 18 cases), high-grade CIN (HCIN, 13 cases) and SCC (17 cases). Paraffin-embedded tissue sections were analyzed for the study. High-risk HPV types were present in 67%, 89% and in 100% of HPV-positive LCIN, HCIN and SCC, respectively (Spearman's correlation coefficient: 0.393, p=0.035). Positive pRb2/p130 expression was detected in 89% of LCIN, 77% of HCIN and in 35% of SCC (p=0.001), whereas diffuse p107 expression was 72%, 62% and 100%, respectively (p=0.024). The results of p53 expression in CINs and SCCs showed values (not statistically significant) comparable with the literature data concerning the antibody D07. For the first time, we tested pRb2/p130 and p107 expressions in CINs and SCCs. We found a progressive decrease in pRb2 expression from CINs to SCCs that suggests an important role of pRb2 in cervical carcinogenesis. Indeed, p107 expression does not seem to be a useful factor. In our opinion, confirmed by the literature data, p53 immunostaining helps to biologically characterize CIN (in particular LCIN) when each case is evaluated separately considering HPV testing/typing.

Accuracy rates of US-guided vacuum-assisted breast biopsy.

A prospective study designed to measure the accuracy of mammography (MRx), ultrasound (US), fine-needle aspiration cytology (FNAC) and one of the most recently introduced techniques, vacuum biopsy (VB), in the diagnosis of breast cancer is reported. A sample of 146 breast lesions on 135 patients were examined. The design of the study made it possible to compare MRx, US, FNAC and VB directly, because it excluded several confounding variables. Statistical indicators--sensitivity, specificity, predictive values (PPV and NPV), false-negative and false-positive rates (FN and FP), suspicious plus indeterminate rate and likelihood ratios (LR)--were calculated. The NPV of MRx and US were remarkably high (92.4% and 97.9%, respectively), confirming previous reports. The complete sensitivity of FNAC was 80%, while specificity was 99.1% and LR of positive tests 88.8. The combined score of FNAC, US and MRx resulted in a good increase in complete sensitivity (97.1%), when compared with the results of the single diagnostic tests evaluated separately. The absolute sensitivity of VB was 97.1% and specificity was 100%. In conclusion, considered together, MRx, US and FNAC appear to be reliable diagnostic procedures and, when they are all negative, the possibility of a cancer is extremely low, although it cannot be completely ruled out. The VB test had the highest absolute sensitivity among all the methods compared. Therefore, this technique could be considered conclusive in diagnostically doubtful cases, avoiding open surgical biopsy.

p53 polymorphism at codon 72 is not a risk factor for cervical carcinogenesis in central Italy.

Recently Storey et al. showed that p53 polymorphism at codon 72 was related to cervical cancer. This polymorphism encodes either arginine (p53Arg) or proline (p53Pro). p53Arg was found to be more susceptible than p53Pro to E6-mediated degradation. Many studies were performed but conclusions are controversial. In this paper, we report our results from 80 women of central Italy, 30 patients showing High-grade Cervical Intraepithelial Neoplasia or squamous cell carcinoma (SCC) and 50 healthy women of the same age. The polymorphism was examined using the Storey's procedure, a molecular method, from formalin-fixed, paraffin-embedded biopsies (patients) and from cytological oral-samples (controls). The distribution of the genotypes among the cases was 27% heterozygous, 27% p53Pro-homozygous and 46% p53Arg-homozygous, while among the controls it was 52%, 2% and 46%, respectively. There was not an increased risk of SCC associated with p53Arg-homozygous; indeed there is a tendency for the contrary (odds ratio, 0.06; 99.4% confidence interval, 0.006-0.63; p = 0.019). Considering: 1) the biological characteristics of p53Pro in vitro; 2) the DNA quality, from formalin-fixed tissue, of our patients; and 3) the small number of samples performed in our study, we can only confirm that p53Pro is not a risk factor in vivo for cervical carcinogenesis in central Italy.

Papillary solid and cystic pancreatic tumor. Genetic prediction factors for malignancy: report of three cases.

BACKGROUND: Papillary solid and cystic pancreatic tumor (PSCPT) is a rare neoplasm of unknown pathogenesis, with an excellent overall prognosis after complete resection. The malignant potential of this tumor remains unclear and was the object of our investigation. PATIENTS AND METHODS: We report three cases of PSCPT submitted to radical resection in which histological and immunohistochemical studies, as well as genetic analysis of Kirsten-ras (K-ras) oncogene mutations, p53 and Fragile Histidine Triad (FHIT) gene expression, were evaluated. RESULTS: Low expression of Ki 67 was consistent with a low karyokinetic index of these tumors. Mutations of the K-ras gene were not present. Low-grade variations of p53, K-ras and FHIT genes were detected by immunohistochemistry. CONCLUSION: PSCPT is a rare neoplasm with low malignancy. Further genetic analysis is required to predict the potential malignancy of this tumor; nevertheless combined multimodality approaches may play a suitable role in identifying more aggressive forms.

Cytological analysis and immunocytochemical expression of Ki67 and Bcl-2 in breast proliferative lesions.

Fine needle aspiration cytology (FNAC) is considered a reliable method for the diagnosis of breast diseases. However, in some cases, cytological diagnosis may be difficult because of the presence of certain cytological parameters, which suggest a proliferative/indeterminate epithelial lesion, ie. a cytological "gray zone" In this retrospective study we considered 37 cases with an uncertain cytological diagnosis and compared the cytological parameters with the histological diagnosis. Furthermore, each case was evaluated with cellular markers such as Ki67 and bcl-2, in order to be able to differentiate the benign from the malignant proliferative breast lumps. Our study showed a correlation between Ki67 expression and malignancy (p<0.001), whereas, no association was observed with decreased or increased bcl-2 activity. Therefore, in our opinion, immunocytochemical Ki67 expression may be helpful in the differentiation of cytologically suspicious/indeterminate breast lesions.