Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing

Demarco, Maria; Carter‐Pokras, Olivia; Hyun, Noorie; Castle, Philip E.; He, Xu; Dallal, Cher M.; Chen, Jie; Gage, Julia C.; Befano, Brian; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine‐Bennett, Tina; Wentzensen, Nicolas; Schiffman, Mark

doi:10.1128/jcm.01910-17

“…Nonetheless, it is important to be aware that screening based solely on hrHPV detection may miss a small fraction of at risk individuals such as the patient described here, where the L1 gene PCR target may be deleted or may lack sufficient sequence homology for recognition. Expanded PCR specificity for HPV analysis is a subject of current interest …”

Section: Discussionmentioning

confidence: 99%

“…Expanded PCR specificity for HPV analysis is a subject of current interest. 86 HPV typing of ICCs currently offers little or no direct benefit to affected patients.…”

Section: Discussionmentioning

confidence: 99%

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Arsdale

¹

,

Patterson

²

,

Maggi

³

et al. 2019

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV‐negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR‐E6‐E7‐E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B‐cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70‐BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV‐associated tumorigenesis.

show abstract

“…Nonetheless, it is important to be aware that screening based solely on hrHPV detection may miss a small fraction of at risk individuals such as the patient described here, where the L1 gene PCR target may be deleted or may lack sufficient sequence homology for recognition. Expanded PCR specificity for HPV analysis is a subject of current interest (71).…”

Section: Discussionmentioning

confidence: 99%

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV-negative cervical cancer

Arsdale

¹

,

Patterson

²

,

Maggi

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV-negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR-E6-E7-E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B-cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70-BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV-associated tumorigenesis. Statement of SignificanceMultiple HPV types have been defined as high risk for cancer causation. However, genomic analyses applied here detected a non-high risk HPV in a carcinoma that was HPV negative, and elucidated virally-associated tumorigenic genetic events. This stresses the importance of thorough genomic analyses for elucidating genetic processes in HPV-associated tumorigenesis. Author SummaryCervical cancer is the second leading cause of cancer death in women worldwide. Most cervical cancers are caused by one of 15 high risk types of human papilloma viruses (HPVs), although hundreds of types of HPVs exist. We used a series of contemporary genomics analyses to examine a cervical cancer that was clinically determined to be HPV-negative.These detected DNA of HPV70, an HPV type not considered to be high risk, in the tumor.Approximately half of the HPV70 DNA genome was present including the viral E6 and E7 oncogenes. Moreover, the viral DNA was inserted into the BCL11B gene in the human genome. BCL11B is known to be mutated in certain human cancers. The HPV70 DNA interacted with the human BCL11B gene to produce altered forms of RNA encoding unusual, truncated forms of the BCL11B protein. These results strongly implicate HPV70 as being oncogenic, suggest that this tumor was caused by a combination of viral oncogenes plus the virally-activated human BCL11B gene, demonstrate novel truncated BCL11B variants with oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate HPV tumorigenesis insights

show abstract

“…In 2006, the European Medicines Evaluation Agency approved two vaccines for use in Europe, as they proved effective by reducing the risk of developing cervical dysplasia. Mass vaccination should be used in girls between 12 -15 years of age, which creates a real opportunity to prevent cervical cancer [102][103][104][105][106][107][108][109][110][111][112][113][114]. Secondary prevention of cancer is mass screening, aimed at early detection of cancer in people without symptoms of the disease and reduction of related mortality.…”

Section: Annals Of Agricultural and Environmental Medicinementioning

confidence: 99%

“…Ultrasound examination is particularly valuable in women with a dense radiological structure of the breast, with a high content of glandular tissue. An additional advantage of this test is its non-invasiveness and harmlessness, which is why it can be performed safely in pregnant women [114][115][116][117][118][119][120][121][122].…”

Section: Annals Of Agricultural and Environmental Medicinementioning

confidence: 99%

Cancer prevention – review paper

Lewandowska¹,

Lewandowski²,

Rudzki³

et al. 2020

Ann Agric Environ Med.

View full text Add to dashboard Cite

Introduction. Every year there is an increase in the number of cases and deaths due to the majority of cancers. Currently, these diseases constitute the second cause of death in Poland and the USA. The number of cases of malignant neoplasms in Poland has more than doubled over the last three decades. According to the National Cancer Registry, in Poland about 95.5 people per thousand die every year from malignant neoplasms. Current epidemiological data on cancer is worrying because the World Health Organization predicts a significant increase in the incidence of cancer in the general population. This problem, which is significant on the global scale, demands the search for more effective prevention methods so that more and more attention is paid to both primary and secondary prevention. Prevention and early detection of cancer have become a priority for the national health policy of many European countries. Numerous studies around the world prove that reducing the risk of cancer is most effective through adopting a healthy lifestyle, avoiding exposure to carcinogens, combined with regular screening. Objective. The aim of the study was to review knowledge on cancer prevention, including the latest research results. Conclusions. Due to the systematic increase in the incidence of cancer, a strong emphasis should be placed on prevention. Preventive actions bring benefits not only to the individual, but are an important aspect of health policy. The importance of primary prevention in relation to healthy people has been demonstrated, including secondary prevention aimed at controlling risk factors in relation to persons exposed to them. The combination of these activities becomes an important element in maintaining the health of the individual, as well as society.

show abstract

Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing

Cited by 25 publications

References 33 publications

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV-negative cervical cancer

Cancer prevention – review paper

Contact Info

Product

Resources

About