scholarly journals Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1846 ◽  
Author(s):  
Adeline Morel ◽  
Cindy Neuzillet ◽  
Maxime Wack ◽  
Sonia Lameiras ◽  
Sophie Vacher ◽  
...  

The role of human papillomavirus (HPV) in anal squamous cell carcinoma (ASCC) carcinogenesis has been clearly established, involving the expression of viral oncoproteins and optional viral DNA integration into the host genome. In this article, we describe the various mechanisms and sites of HPV DNA insertion and assess their prognostic and predictive value in a large series of patients with HPV-positive ASCC with long-term follow-up. We retrospectively analyzed 96 tumor samples from 93 HPV-positive ASCC patients using the Capture-HPV method followed by Next-Generation Sequencing, allowing determination of HPV genotype and identification of the mechanisms and sites of viral genome integration. We identified five different mechanistic signatures of HPV insertions. The distribution of HPV signatures differed from that previously described in HPV-positive cervical carcinoma (p < 0.001). In ASCC samples, the HPV genome more frequently remained in episomal form (45.2%). The most common signature of HPV insertion was MJ-SC (26.9%), i.e., HPV–chromosomal junctions scattered at different loci. Functionally, HPV integration signatures were not associated with survival or response to treatment, but were associated with viral load (p = 0.022) and PIK3CA mutation (p = 0.0069). High viral load was associated with longer survival in both univariate (p = 0.044) and multivariate (p = 0.011) analyses. Finally, HPV integration occurred on most human chromosomes, but intragenic integration into the NFIX gene was recurrently observed (n = 4/51 tumors). Overall, the distribution of mechanistic signatures of HPV insertions in ASCC was different from that observed in cervical carcinoma and was associated with viral load and PIK3CA mutation. We confirmed recurrent targeting of NFIX by HPV integration, suggesting a role for this gene in ASCC carcinogenesis.

2012 ◽  
Vol 50 (1) ◽  
pp. 87-94
Author(s):  
Masahiro Hasegawa ◽  
Zeyi Deng ◽  
Hiroyuki Maeda ◽  
Yukashi Yamashita ◽  
Sen Matayoshi ◽  
...  

Background: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP). Methods: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group). Results: The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration. Conclusions: HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.


2006 ◽  
Vol 16 (3) ◽  
pp. 1048-1054 ◽  
Author(s):  
R. K. Singh ◽  
S. Maulik ◽  
S. Mitra ◽  
R. K. Mondal ◽  
P. S. Basu ◽  
...  

To understand the role of human papillomavirus (HPV) in recurrence of uterine cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18, 14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV-positive exfoliated cells (positive predictive value, 100%; negative predictive value, 27%) with concordance in HPV types. The recurrence of the disease was significantly associated with the presence of HPV in the exfoliated cell (P = 0.01) and plasma (P = 0.007) as well as high viral load in the exfoliated cell (P = 0.0002). Kaplan–Meier disease-free estimates have also shown the significant association between HPV prevalence in plasma and recurrence of the disease (P = 0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high viral load in the exfoliated cell as well as HPV presence in the plasma samples could be used in early detection of the patients at increased risk for disease recurrence and progression.


2012 ◽  
Vol 50 (1) ◽  
pp. 87-94
Author(s):  
Masahiro Hasegawa ◽  
Zeyi Deng ◽  
Hiroyuki Maeda ◽  
Yukashi Yamashita ◽  
Sen Matayoshi ◽  
...  

Background: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP). Methods: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group). Results: The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration. Conclusions: HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.


2014 ◽  
Vol 39 (2) ◽  
pp. 86-90 ◽  
Author(s):  
T Rahman ◽  
S Tabassum ◽  
M Jahan ◽  
A Nessa ◽  
Dr Ashrafunnessa

Human papillomavirus (HPV) high risk genotype infection and HPV viral load influences the development of invasive cervical cancer and cervical intra-epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may play a potential role in its early detection and management. The present study detected HPV DNA and estimated HPV viral load in different types of cervical lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases were positive for HPV DNA. The highest viral load (501 x 10³ copies/ml) was detected in a patient with invasive carcinoma, while the lowest viral load (105 x 10³ copies/ml) was detected from a case of chronic cervicitis. The mean viral load in CIN I was 119.25 x 10³±12.5 x 10³ copies/ml (range: 110 x 10³ - 137 x 10³) and 208.50 x 10³ ± 0.59 x 10³ copies/ml (range: 139 x 10³-305 x 10³) in CIN II / III. Interestingly, HPV DNA was detected from a patient with normal cytological findings. Our study observed a moderate presence of high-risk HPV genotypes among women with cervical lesions. The HPV viral load varied with the age of the patients and stage of cervical lesions. The HC2 assay is a promising tool for diagnosing high-risk HPV infection especially before cytology tests show any abnormality. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19648 Bangladesh Med Res Counc Bull 2013; 39: 86-90


Virology ◽  
2010 ◽  
Vol 399 (1) ◽  
pp. 129-133 ◽  
Author(s):  
Anja Köhler ◽  
Marc Gottschling ◽  
Jana Förster ◽  
Joachim Röwert-Huber ◽  
Eggert Stockfleth ◽  
...  

Immunology ◽  
2015 ◽  
Vol 146 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Thiago Theodoro Martins Prata ◽  
Camila Mareti Bonin ◽  
Alda Maria Teixeira Ferreira ◽  
Cacilda Tezelli Junqueira Padovani ◽  
Carlos Eurico dos Santos Fernandes ◽  
...  

2020 ◽  
Author(s):  
Yang Liu ◽  
Changjun Xu ◽  
Jing Pan ◽  
Chunyi Sun ◽  
Honglin Zhou

Abstract Background: The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk (HR)-HPV viral load and different cervical lesion degrees.Methods: This was a retrospective study of the patients who first visited the hospital between January 2015 and June 2018. Patients with positive HR-HPV were screening for cervical cancer. The HR-HPV DNA load was measured by the second generation hybrid capture (HC2) technology. The patients grouped as normal, CIN I, CIN II, CIN III, and cervical cancer. Multivariable logistic regression was performed to explore the association between HR-HPV DNA load and cervical lesions.Results: Finally, 265 patients were grouped as normal (n=125), CIN I (n=51), CIN II (n=23), CIN III (n=46), and cervical cancer (n=20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN I (CIN I: OR=3.959, 95%CI: 1.300-12.059, P=0.015) CIN II (OR=6.211, 95%CI: 1.641-23.513, P=0.007), CIN III (OR=7.002, 95%CI: 2.308-21.244, P=0.001), and cervical cancer (OR=9.439, 95%CI: 2.394-37.22, P=0.001).Conclusion: Cervical lesions are closely related to HR-HPV infection. Higher HR-HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.


2020 ◽  
Vol 14 (1) ◽  
pp. 57-64
Author(s):  
Ashraf I. Khasawneh ◽  
Nisreen Himsawi ◽  
Jumana Abu-Raideh ◽  
Muna Salameh ◽  
Niveen Abdullah ◽  
...  

Background: In addition to smoking and alcohol consumption, human papillomavirus (HPV) is a leading etiology for Head and Neck Squamous Cell Carcinoma (HNSCC). However, this causal association is still understudied in Middle Eastern populations. Objective: The aim of this study was to determine the prevalence of HPV-associated infection in the Jordanian HNSCC patients and the associated HPV genotypes. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) squamous cell carcinoma samples of the head and neck were collected from two referral centers in Amman, Jordan to determine the existence of HPV DNA. After DNA extraction HPV infection and genotyping were identified using real-time PCR. Results: HPV DNA was detected in 19 out of 61 (31.1%) HNSCC samples. Despite screening for 28 different genotypes, HPV 16 was the only genotype identified in all examined samples. Most HPV-positive samples were obtained from the oropharynx (41.7%), oral cavity (37%), and larynx (18.2%). No significant association between HPV 16 genotype and age, sex, tobacco use, anatomical location, or tumor grade was noticed. Conclusion: This study reported a high association between HPV 16 genotype and HNSCC in Jordanian patients. These data should facilitate the implementation of appropriate HPV awareness campaigns, and activate selective prophylactic measures against HPV infection.


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