scholarly journals Comprehensive multiomic characterization of human papillomavirus-driven recurrent respiratory papillomatosis reveals distinct molecular subtypes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cem Sievers ◽  
Yvette Robbins ◽  
Ke Bai ◽  
Xinping Yang ◽  
Paul E. Clavijo ◽  
...  

AbstractRecurrent respiratory papillomatosis (RRP) is a debilitating neoplastic disorder of the upper aerodigestive tract caused by chronic infection with low-risk human papillomavirus types 6 or 11. Patients with severe RRP can require hundreds of lifetime surgeries to control their disease and pulmonary papillomatosis can be fatal. Here we report the comprehensive genomic and transcriptomic characterization of respiratory papillomas. We discovered and characterized distinct subtypes with transcriptional resemblance to either a basal or differentiated cell state that associate with disease aggressiveness and differ in key molecular, immune and APOBEC mutagenesis profiles. Through integrated comparison with high-risk HPV-associated head and neck squamous cell carcinoma, our analysis revealed divergent molecular and immune papilloma subtypes that form independent of underlying genomic alterations. Cumulatively our results support the development of dysregulated cellular proliferation and suppressed anti-viral immunity through distinct programs of squamous cell differentiation and associated expression of low-risk HPV genes. These analyses provide insight into the pathogenesis of respiratory papillomas and provide a foundation for the development of therapeutic strategies.

Tumor Biology ◽  
2010 ◽  
Vol 32 (2) ◽  
pp. 409-416 ◽  
Author(s):  
José Vieira de Spíndula-Filho ◽  
Aparecido Divino da Cruz ◽  
Angélica Ferreira Oton-Leite ◽  
Aline Carvalho Batista ◽  
Cláudio Rodrigues Leles ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (49) ◽  
pp. 86369-86383 ◽  
Author(s):  
Nene N. Kalu ◽  
Tuhina Mazumdar ◽  
Shaohua Peng ◽  
Li Shen ◽  
Vaishnavi Sambandam ◽  
...  

2012 ◽  
Vol 93 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Maria Lidqvist ◽  
Olle Nilsson ◽  
Jan Holmgren ◽  
Sebastian Hölters ◽  
Eva Röijer ◽  
...  

The selection and characterization of a set of mouse mAbs against high-risk human papillomavirus (HPV) E7 oncoprotein and the development of protocols for immunocytochemistry (ICC) are described here. A large number of antibodies raised towards HPV16 and 18 E7 were tested for high-risk specificity by ELISA using a panel of HPV E7 proteins. Antibodies detecting low-risk E7 were discarded, resulting in 38 high-risk HPV E7-specific antibodies. The corresponding epitopes were mapped using overlapping HPV E7 fragments displayed on phage particles. Functionality in ICC against formalin-fixed cervical cancer cell lines was demonstrated for ten mAbs; their high-risk specificity was confirmed by Western blot analysis and ICC on transiently transformed cells expressing high- or low-risk HPV E7. These mAbs were specific for one or several of the high-risk strains HPV16, 18, 31, 35 and 45. Specific E7 staining of liquid-based cytology (LBC) samples was demonstrated for seven mAbs and optimized protocols were established. The E716-41 and E718-79 mAbs demonstrated particularly strong and specific staining of cells stored in LBC fluid for at least 6 months. It is proposed that the high-risk HPV E7 staining protocols established in this study may have the potential to be included in a complementary test for the detection and identification of malignantly transformed cells, in for example atypical squamous cells of undetermined significance samples.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e17017-e17017
Author(s):  
Damien Urban ◽  
June Corry ◽  
Benjamin J. Solomon ◽  
Annette May Ling Lim ◽  
Tsien Fua ◽  
...  

2007 ◽  
Vol 96 (10) ◽  
pp. 1554-1559 ◽  
Author(s):  
K Shuyama ◽  
A Castillo ◽  
F Aguayo ◽  
Q Sun ◽  
N Khan ◽  
...  

2000 ◽  
Vol 38 (1) ◽  
pp. 408-411
Author(s):  
József Kónya ◽  
György Veress ◽  
Attila Juhász ◽  
Krisztina Szarka ◽  
Tamás Sápy ◽  
...  

ABSTRACT The type specificity of the human papillomavirus (HPV) Hybrid Capture Tube (HCT) test was evaluated by using typing with PCR (MY09-MY11)-restriction fragment length polymorphism (RFLP) and sequencing. All samples HCT test positive for only low-risk HPV ( n = 15) or only high-risk HPV ( n = 102) were confirmed, whereas 9 of 12 HCT test double-positive samples contained only high-risk HPV types as determined by PCR-RFLP. Several high-risk HPV types (HPV-53, -58, -62, -66, -CP8304, and -MM4) not included in the HCT test were indeed detected, indicating a broader detection range with retained distinction between low-risk and high-risk HPV types.


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