Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study

Background Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. Methods Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. Findings Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. Interpretation Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years

Programa nacional de prevención y consejería genética del retinoblastoma mediante detección de mutaciones en el gen rb.

El retinoblastoma es un raro tumor ocular que se diagnostica en los niños, 40% de los casos se consideran hereditarios y 60% esporádicos. El modelo genético propuesto por Knudson involucrauna la doble mutación inactivante del gen Rb, exclusivamente somática en los esporádicos y germinal más somática en los hereditarios. Esta investigacin tuvo como objetivo caracterizar las mutaciones en el gen Rb mediante secuenciación directa y evaluar su utilidad en la consejería genética

Programa nacional de prevención y consejería genética del retinoblastoma mediante detección de mutaciones en el gen RB.

El retinoblastoma es un raro tumor ocular que se diagnostica en los niños, 40% de los casos se consideran hereditarios y 60% esporádicos. El modelo genético propuesto por Knudson involucra una la doble mutación inactivante del gen Rb, exclusivamente somática en los esporádicos y germinal más somática en los hereditarios. Esta investigacin tuvo como objetivo caracterizar las mutaciones en el gen Rb mediante secuenciación directa y evaluar su utilidad en la consejería genética

HPV-16 E6 L83V variant in squamous cell carcinomas of the upper aerodigestive tract

PURPOSE: The aim of this prospective case series study was to determine the prevalence of HPV-DNA, analyze the E6 mRNA expression, identify intra-type variation in the E6 oncogene in upper aerodigestive tract (UADT) squamous cell carcinoma (SCC), and correlate the presence of HPV-DNA with several clinical parameters and outcome. METHODS: Frozen samples of UADT-SCC were analyzed for the presence and characterization of HPV-DNA and RNA sequences by means of polymerase chain reaction (PCR), reverse transcriptase-PCR, and direct sequencing of amplified products. RESULTS: HPV-DNA sequences were detected in 10% of the tumors, all of which were typed as HPV-16. Positivity for HPV-16 E6/E7 mRNA was observed in five of the eight HPV-positive tumors (62.5%). The HPV-16 E6 L83V variant was present in five cases. Multivariate analysis identified a history of absence of smoking (P = 0.009) as a predictor of HPV-positive tumor. No significant differences in overall and disease free survival curves were observed between patients with HPV-positive tumors and patients with tumors without detectable HPV-DNA. CONCLUSION: Our findings support the etiological participation of HPV-16 in a subset of UADT-SCCs from patients lacking traditional risk factors. The potential prognostic significance of HPV-16 E6 L83V variant in HPV-16 positive UADT-SCCs should be more extensively investigated

Age-independent increasing prevalence of Human Papillomavirus-driven oropharyngeal carcinomas in North-East Italy

HPV-driven oropharyngeal carcinomas (OPCs) show geographical variations with increasing temporal trends in several areas. We investigated their frequency and clinical outcomes within a prospective multicenter cohort study in North-East Italy. A tumor was defined as HPV-driven by using at least two different biomarkers, usually HPV-DNA positivity and p16INK4A overexpression. Different survival outcomes were compared among patients with HPV-driven and non-HPV-driven tumors. Overall, 42/130 (32.3%) patients with newly diagnosed OPC during the period 2000\u20132018 resulted HPV-driven; HPV16 was involved in 37 cases (88%), HPV33 in 3 cases (7%), HPV58 and HPV18 in 1 case each. Over time, HPV-driven cases raised from 16.7% (6/36) during 2000\u20132006 to 46.1% (24/52) during 2013\u20132018 (p < 0.001). The increase in HPV-driven OPCs was more marked in females than males (p = 0.010), and the frequency of HPV-driven cases was similar in the different age groups. In comparison to cases with non-HPV-driven tumors, a significantly (p < 0.001) better progression-free and overall survival were recorded among patients affected by HPV-driven OPC. The prevalence of HPV-driven OPC cases has been significantly increasing during the last two decades also in North-East Italy and was associated with favorable outcome. OPCs driven by non-HPV16 oncogenic types were restricted to patients older than 68-yrs

Oral human papillomavirus and human herpesvirus-8 infections among human immunodeficiency virus type 1-infected men and women in Italy.

Background: Oral human papillomavirus (HPV) and human herpesvirus-8 (HHV8) infections are sexually transmitted and respectively associated with the development of oropharyngeal carcinoma and Kaposi sarcoma. The aim of the study was to evaluate HPV prevalence and its possible correlation with HHV8 oral shedding, in relation to sex, human immunodeficiency virus (HIV) behavioral risk factor, and immune function. Methods: The study population comprised 100 HIV-infected individuals divided into 3 groups: (1) 38 men who have sex with men (MSM), (2) 24 heterosexual men, and (3) 38 women. DNA was obtained from cells of unstimulated whole saliva. Human papillomavirus sequences were searched for by polymerase chain reaction (PCR) with MY09/MY11 primers or by nested PCR with GP5+/GP6+ primers as the second step. Typing was accomplished by restriction fragment length polymorphism analysis or by direct sequencing or by reverse line blot. Human herpesvirus-8 sequences were detected and quantified by nested PCR and real-time PCR, respectively. Results: Oral HPV infection was present in 37 (prevalence, 37%) of 100 (13 with high-risk and 24 with low-risk types) patients; the most frequent types were HPV16, HPV6, HPV10, HPV61, HPV66, and HPV83. Human herpesvirus-8 DNA was detected in 46 (46%) of 100 subjects. Both infections had the highest prevalence among MSM and the lowest among women; women had a lower prevalence of high-risk HPV types than did both male groups (P = 0.05). An inverse correlation was observed with concomitant oral HHV8 infection (P = 0.007). Conclusions: High prevalence of oral HPV and HHV8 infections was observed; MSM had the highest figures, despite better control of HIV infection

Extensive anal condylomatosis: prognosis in relation to viral and host factors.

To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful

Oral human papillomavirus and human herpesvirus-8 infections among human immunodeficiency virus type 1-infected men and women in Italy.

Background: Oral human papillomavirus (HPV) and human herpesvirus- 8 (HHV8) infections are sexually transmitted and respectively associated with the development of oropharyngeal carcinoma and Kaposi sarcoma. The aim of the study was to evaluate HPV prevalence and its possible correlation with HHV8 oral shedding, in relation to sex, human immunodeficiency virus (HIV) behavioral risk factor, and immune function. Methods: The study population comprised 100 HIV-infected individuals divided into 3 groups: (1) 38 men who have sex with men (MSM), (2) 24 heterosexual men, and (3) 38 women. DNA was obtained from cells of unstimulated whole saliva. Human papillomavirus sequences were searched for by polymerase chain reaction (PCR) with MY09/MY11 primers or by nested PCR with GP5+/GP6+ primers as the second step. Typing was accomplished by restriction fragment length polymorphism analysis or by direct sequencing or by reverse line blot. Human herpesvirus- 8 sequences were detected and quantified by nested PCR and real-time PCR, respectively. Results: Oral HPV infection was present in 37 (prevalence, 37%) of 100 (13 with high-risk and 24 with low-risk types) patients; the most frequent types were HPV16, HPV6, HPV10, HPV61, HPV66, and HPV83. Human herpesvirus-8 DNA was detected in 46 (46%) of 100 subjects. Both infections had the highest prevalence among MSM and the lowest among women; women had a lower prevalence of high-risk HPV types than did both male groups (P = 0.05). An inverse correlation was observed with concomitant oral HHV8 infection (P = 0.007). Conclusions: High prevalence of oral HPV and HHV8 infections was observed; MSM had the highest figures, despite better control of HIV infection

A 3-year interval is too short for re-screening HPV negative women: a population-based cohort study

none11To compare the results of the first round and of re-screening 3 years after a negative human papillomavirus (HPV) test in women attending two HPV-based screening programs.noneZorzi, Manuel; Frayle, Helena; Rizzi, Martina; Fedato, Chiara; Rugge, Massimo; Penon, Maria Gabriella; Bertazzo, Alessandra; Callegaro, Susanna; Campagnolo, Marisa; Ortu, Fausta; Del Mistro, AnnarosaZorzi, Manuel; Frayle, Helena; Rizzi, Martina; Fedato, Chiara; Rugge, Massimo; Penon, Maria Gabriella; Bertazzo, Alessandra; Callegaro, Susanna; Campagnolo, Marisa; Ortu, Fausta; DEL MISTRO, Annaros