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

Cervical cancer screening by high risk HPV testing in routine practice: results at one year recall of high risk HPV-positive and cytology-negative women

Abstract OBJECTIVE: Cervical cancer screening by human papillomavirus (HPV) testing requires the use of additional triage and follow-up analyses. We evaluated women's compliance with and the performance of this strategy in a routine setting. SETTING: Five cervical service screening programmes in North-East Italy. METHODS: Eligible women aged 25-64 invited for a new screening episode underwent HPV testing for high risk types (hrHPV by Hybrid Capture 2) and cytology triage. Women with positive HPV and cytology results were referred for colposcopy; women with positive HPV but negative cytology results were referred to 1-year repeat hrHPV testing. RESULTS: Of 46,694 women screened by HPV testing up to December 2011, 3,211 (6.9%) tested hrHPV positive; 45% of these had a positive triage cytology. Those with negative cytology were invited for 1-yr repeat testing. Compliance with invitation was 61.6% at baseline and 85.3% at 1-yr repeat. Rate of persistent hrHPV positivity was 58% (830/1,435). Colposcopy performed in women with a positive hrHPV test at 1-yr repeat accounted for 36% of all colposcopies performed within the screening programmes. Cumulatively, a histological high-grade lesion was detected in 276 women (5.9‰ detection rate), 234 at baseline (85%), and 42 (15%) at 1-yr repeat. CONCLUSIONS: Compliance with hrHPV-based screening programmes was high both at baseline and at 1-yr repeat. Compared with the randomized trials, a higher proportion of triage cytology was read as positive, and only a small number of high-grade lesions were detected among the group of hrHPV positive cytology negative women who repeated testing 1-yr after baseline

A retrospective cohort study of young women spontaneously choosing to be vaccinated against hpv: Outcomes from their first cervical cancer screening test

Background: Efficacy for cervical cancer prevention of opportunistic HPV vaccination in post-pubertal girls is lower than in 11-year-olds. Methods: Women born between 1986 and 1992 vaccinated at 15–25 years of age (at least one dose of 4-valent HPV vaccine) and screened at 24–27 years of age were included. Frequency of opportunistic vaccination, overall and by birth cohort, was calculated; screening outcomes were compared between vaccinated and unvaccinated women. Results: Overall, 4718 (4.9%) HPV-vaccinated, and 91,512 unvaccinated, women were studied. The frequency of vaccination increased by birth cohort, ranging between 1.8% and 9.8%; age at vaccination decreased progressively by birth cohort (p &lt; 0.0001). Participation in screening was 60.8% among vaccinated, and 56.6% among unvaccinated, women (p &lt; 0.0001). Detection rates (DR) for high-grade lesions were lower in vaccinated women (2.11‰ vs. 3.85‰ in unvaccinated, for CIN3+, p = 0.24; 0.0‰ vs. 0.22‰ for cancer). The DR of CIN3+ increased with age at vaccination, scoring respectively 0.0‰, 0.83‰, and 4.68‰ for women vaccinated when they were 15–16, 17–20, and 21–25 years old (p = 0.17). Conclusions: In comparison to unvaccinated women, higher compliance with cervical cancer screening invitation and lower CIN3+ DR among vaccinated women was observed. Age at vaccination was inversely correlated to vaccination efficacy

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 2000–2018 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 2000–2006 to 46.1% (24/52) during 2013–2018 (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

Performance of HPV E6/E7 mRNA assay as primary screening test: Results from the NTCC2 trial

As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives was also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment. Of the 41 127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared with HPV DNA. The weighted specificity estimate fo