scholarly journals Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hélène Péré ◽  
Raphael Vernet ◽  
Simon Pernot ◽  
Juliette Pavie ◽  
Nicolas Robillard ◽  
...  

AbstractArchival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

2020 ◽  
Vol 10 ◽  
Author(s):  
Jie Qian ◽  
Rongrong Chen ◽  
Ruiying Zhao ◽  
Yuchen Han ◽  
Yongfeng Yu

BackgroundThis study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.MethodsWe retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.ResultsOf 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.ConclusionsSignificant differences exist among three subtypes of LUSC in molecular characterizations.


2016 ◽  
Vol 61 (6) ◽  
pp. 275-279
Author(s):  
O. Yu. Dvoryaninova ◽  
E. G. Nikitina ◽  
V. A. Bychkov ◽  
N. V. Litviakov

The article describes methods for the human papillomavirus (HPV) detection in tumor and adjacent (morphologically intact) tissues of patients with laryngeal squamous cell carcinoma (LSSC) in terms of viral pathogenesis. Comparative evaluation of the principles and techniques for HPV detection was performed. Advantages and disadvantages of the HPV detection methods are described. Approaches for DNA and HPV oncoproteins E6-E7 identification are substantiated. The results of our research into the qualitative and quantitative detection of HPV in the tumor and adjacent tissues of patients with Lssc are described. The research was conducted using commercial test systems Amplisens HPV HR screen-titre-FL and Amplisens HPV HR genotype-FL. Based on these results we developed the algorithm of HPV detection in samples of tumor tissue of patients with Lssc. The need for typing HPV-positive tissue samples with low concentration of HPV DNA was discussed.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 735-735
Author(s):  
Jaymin Jhaveri ◽  
Lael Rayfield ◽  
Yuan Liu ◽  
Mudit Chowdhary ◽  
Richard John Cassidy ◽  
...  

735 Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation in the National Cancer Database (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n = 498, 46.8%) and HPV- (n = 565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR 0.60, CI 0.38-0.96; p = 0.034). However, for women, HPV infection did not significantly influence survival (HR 1.47, CI 0.96-2.25; p = 0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17004-e17004
Author(s):  
Teerapat Ungtrakul ◽  
Somboon Keelawat ◽  
Chanida Vinayanuwattikun ◽  
Virote Sriuranpong

e17004 Background: HPV-associated head and neck squamous cell carcinoma (HNSCC) seems to increase during the last decades and has been commonly described to associate with younger patients. However the true prevalence of HPV in this specific population remains unclear. Methods: We collected archival 56 paraffin-embedded tumor tissue samples from HNSCC patients diagnosed and treated at King Chulalongkorn Memorial Hospital between 2000 and 2010. The major inclusion criterion was the age at diagnosis less than 45 year-old. HPV status was determined by HPV polymerase chain reaction (PCR) with degenerated primer covered over 37 HPV serotypes including high-risk HPV6, 11, 16, 18, 31 and 33. Additional immunohistochemical stain (IHC) of p16 was performed. The clinicopathological correlations with HPV status were analyzed. Results: Fourteen (25%) of the 56 HNSCC samples exhibited HPV DNA by PCR. Among cancer sites, 7 of 23 (30%) oral cavity, 3 of 11 (27%) oropharynx, and 4 of 22 (18%) hypopharynx and larynx primary organs displayed HPV DNA in tumor tissues. There was no major difference in the demographic data, tumor characteristics and treatment modalities between HPV DNA-negative and HPV DNA-positive samples. HPV DNA-positive tumors tended to have a better 2-year overall survival when compared with HPV DNA-negative tumors (66 and 40 percent, respectively) (p=0.10). After adjusted for independent prognostic variables of cigarette smoking, alcohol consumption, site of primary tumor and nodal status, only HPV DNA status was a predictor for a better survival (HR 0.16; 95%CI, 0.01-0.66). Additional IHC for p16 expression revealed 8 of 48 (16%) of p16 overexpression with twenty-two percent concordant rate with HPV PCR. Conclusions: Though HPV genome was moderately found in our young HNSCC patients, HPV DNA was not associated with a significant better survival in the primary analysis. Nevertheless, multivariate analysis adjusting for prognostic variables demonstrated a significant better prognosis in HPV DNA-positive tumors in this subset of HNSCC. Low concordant rate between HPV DNA and p16 overexpression in these young populations may caution the use of p16 overexpression as a surrogate marker of HPV.


Sign in / Sign up

Export Citation Format

Share Document