Dataset Information

HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant.

ABSTRACT: INTRODUCTION:Recurrent cervical intraepithelial lesions (rCIN2/3) after treatment of CIN2/3 occur in 5-15% of cases. rCIN2/3 can result from incomplete resection of CIN2/3, where the same HPV type and variant remains present. rCIN2/3 could also occur following a new infection with a different HPV variant of the same HPV type as the initial lesion. This study investigates HPV16 consensus variants in paired HPV16 positive scrapes from baseline CIN2/3 and rCIN2/3 lesions. METHODS:Paired HPV16 positive cervical scrapes of women with CIN2/3?at baseline and rCIN2/3 6 or 12 months after treatment were selected for whole-genome amplification and Illumina sequencing. Sequences were compared and nucleotide changes over time were characterized. RESULTS:From 14 paired samples, 10 had identical consensus variants in baseline CIN2/3 and rCIN2/3. Four paired samples showed one to three nucleotide variations at recurrent disease compared to baseline. CONCLUSION:Identical or nearly identical HPV16 consensus variants were found in scrapes of paired HPV16 positive baseline CIN2/3 and rCIN2/3 lesions after treatment, suggesting no need for HPV variant analysis when the same HPV type is found in both lesions. These results argue for either incomplete excision of baseline CIN2/3 or inability of clearance of the original HPV infection.

SUBMITTER: van der Weele P

PROVIDER: S-EPMC6477513 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant.

van der Weele Pascal P King Audrey J AJ Meijer Chris J L M CJLM Steenbergen Renske D M RDM

Papillomavirus research (Amsterdam, Netherlands) 20190413

<h4>Introduction</h4>Recurrent cervical intraepithelial lesions (rCIN2/3) after treatment of CIN2/3 occur in 5-15% of cases. rCIN2/3 can result from incomplete resection of CIN2/3, where the same HPV type and variant remains present. rCIN2/3 could also occur following a new infection with a different HPV variant of the same HPV type as the initial lesion. This study investigates HPV16 consensus variants in paired HPV16 positive scrapes from baseline CIN2/3 and rCIN2/3 lesions.<h4>Methods</h4>Pai ...[more]

PMID: 30991124

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Project description:BackgroundHuman papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma.MethodsPatients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFN?-ELISPOT.ResultsNo systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFN?, TNF?, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease.ConclusionsThe HPV16-SLP vaccine was well tolerated and induced a broad IFN?-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.

Project description:BackgroundMolecular diagnosis of Inherited Retinal Dystrophies (IRD) has long been challenging due to the extensive clinical and genetic heterogeneity present in this group of disorders. Here, we describe the clinical application of an integrated next-generation sequencing approach to determine the underlying genetic defects in a Spanish family with a provisional clinical diagnosis of autosomal recessive Retinitis Pigmentosa (arRP).ResultsExome sequencing of the index patient resulted in the identification of the homozygous BBS1 p.M390R mutation. Sanger sequencing of additional members of the family showed lack of co-segregation of the p.M390R variant in some individuals. Clinical reanalysis indicated co-ocurrence of two different phenotypes in the same family: Bardet-Biedl syndrome in the individual harboring the BBS1 mutation and non-syndromic arRP in extended family members. To identify possible causative mutations underlying arRP, we conducted disease-targeted gene sequencing using a panel of 26 IRD genes. The in-house custom panel was validated using 18 DNA samples known to harbor mutations in relevant genes. All variants were redetected, indicating a high mutation detection rate. This approach allowed the identification of two novel heterozygous null mutations in RP1 (c.4582_4585delATCA; p.I1528Vfs*10 and c.5962dupA; p.I1988Nfs*3) which co-segregated with the disease in arRP patients. Additionally, a mutational screening in 96 patients of our cohort with genetically unresolved IRD revealed the presence of the c.5962dupA mutation in one unrelated family.ConclusionsThe combination of molecular findings for RP1 and BBS1 genes through exome and gene panel sequencing enabled us to explain the co-existence of two different retinal phenotypes in a family. The identification of two novel variants in RP1 suggests that the use of panels containing the prevalent genes of a particular population, together with an optimized data analysis pipeline, is an efficient and cost-effective approach that can be reliably implemented into the routine diagnostic process of diverse inherited retinal disorders. Moreover, the identification of these novel variants in two unrelated families supports the relatively high prevalence of RP1 mutations in Spanish population and the role of private mutations for commonly mutated genes, while extending the mutational spectrum of RP1.

Dataset Information

HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant.

Publications

HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant.

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