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Abstract Background This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies. Methods Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. Results 3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%). In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005). The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085). Conclusions Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there.

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.

Objective: To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening Setting: Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). Methods: The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. Results: HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3‰ vs. 3.4‰). Conclusions: HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an "anticipatory effect" in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process. [ABSTRACT FROM AUTHOR]

Given the clinical similarity with oral condyloma, it is important to differentiate FEH from other oral HPV-related lesions that may be acquired following sexual abuse.[[3], [5]] The diagnosis is often based only on clinical presentation because histopathology does not show specific findings, as in our case. We performed an oral swab for HPV detection and typing to exclude a sexually transmitted infection; the test resulted in negative for all 28 detectable HPV strains (Anyplex II HPV 28 Detection System). We present a case of Heck's disease, also known as focal epithelial hyperplasia (FEH), in a 12-year-old Peruvian girl, otherwise healthy, referred to our Dermatology Clinic for evaluation of multiple asymptomatic lesions progressively arising in her oral cavity in the last 3 years. [Extracted from the article]

In sporadic schwannomas, inactivation of both copies of the NF2 tumor suppressor gene on 22q is common. Constitutional mutations of SMARCB1 are responsible of schwannomatosis, an inherited tumor predisposition syndrome, characterized by the development of multiple schwannomas. We analysed the frequency of copy number changes on chromosome 22 and the mutation of NF2 and SMARCB1 in 26 sporadic schwannomas. We found two spinal schwannomas with an identical somatic missense mutation in SMARCB1 exon 9: p.(Arg377His). Both SMARCB1 mutated schwannomas had LOH of 22q and one of them harbored an inactivating mutation of NF2. The p.(Arg377His) change was not found in a series of 28 vestibular schwannomas. Our data indicate that mutations affecting SMARCB1 play a role in the development or progression of a small subset of spinal schwannomas and that biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function in schwannoma tumorigenesis according to the “four-hit/three events” mechanism of tumorigenesis that we demonstrated in schwannomatosis-associated schwannomas. [ABSTRACT FROM AUTHOR]

Background: This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies. Methods: Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. Results: 3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%). In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005). The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085). Conclusions: Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there. [ABSTRACT FROM AUTHOR]

Background: This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies., Methods: Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11., Results: 3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%).In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005).The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085)., Conclusions: Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there.