Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Taejung

doi:10.7150/ijms.5585

Cited by 16 publications

(14 citation statements)

References 32 publications

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“…The differences in clinical performance among the commercially available HPV assays may identify unique subsets of women with very different risk profiles, especially between assays targeting HPV L1-DNA and HPV E6/E7-mRNA. It has been documented that the HPV L1 capsid protein is significantly lower or negative in women with high-grade cervical lesions25 or disease progression 26. Conversely, HPV 16/18 E6/E7 oncoproteins were significantly higher in cervical tissue with high-grade squamous intraepithelial lesions 27.…”

Section: Discussionmentioning

confidence: 99%

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

Christensen

Luna³

et al. 2019

Int J Gynecol Cancer

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ObjectiveHuman papilloma virus (HPV) detection and genotyping are increasingly used in clinical risk assessment. We aimed to analyze HPV genotyping performance in risk stratification among cytology diagnosis categories.MethodsBetween January 1, 2015 and December 31, 2016, 4562 cases with cytology–HPV co-testing and biopsy follow-up were identified. HPV tests were performed on Cobas (n=3959) or Aptima (n=603) platforms. Of the biopsies, 669 demonstrated high-grade squamous intraepithelial lesions or worse.ResultsPooled high-risk HPV testing had high overall sensitivity (97%) but low specificity (20%) and positive predictive value (20%) for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. HPV16/18 genotyping had considerably improved specificity (81%) and positive predictve value (35%) in predicting high-grade squamous intraepithelial lesions or worse, especially in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion categories. Significantly more biopsy-confirmed high-grade squamous intraepithelial lesions or worse were detected by Aptima than Cobas testing, as measured by HPV16/18 (48% vs 33%, p<0.001), non-16/18 high-risk HPV (18% vs 13%, p=0.029), or all high-risk HPV genotypes (27% vs 19%, p<0.001). Aptima genotyping showed a significantly higher positive predictive value than Cobas genotyping for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in the atypical squamous cells of undetermined significance category (47% vs 23%, p<0.05).ConclusionsHPV genotyping was sensitive for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in all cytologic categories, and is particularly valuable in risk evaluation for women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The triaging role was greatly diminished in high-risk lesions (atypical glandular cells, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions) due to low specificity and positive predictive value. Aptima performance in risk management was superior to Cobas, with significantly higher positive predictive value for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. Our results highlight the importance of careful data interpretation from studies using different HPV testing methods and the need to incorporate HPV E6/E7-mRNA testing into management guidelines.

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Section: Discussionmentioning

confidence: 99%

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

Christensen

Luna³

et al. 2019

Int J Gynecol Cancer

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“…The abortion of hrHPV cycles in HSIL results in the L1 capsid protein being non-detectable (55). From the immunological perspective, hrHPV L1 is the inducer for the CD8 + and CD4 + T cell response against hrHPV infection (56).…”

Section: Immune-related Markers Of Cin and Cervical Cancermentioning

confidence: 99%

“…HPV16, 18,31,33,35,39,45,51,52,56,58,59, 68 and 69 are classified as the hrHPVs (5). HPV6, 11,40,42,54,55,61,62,64,71,72,81,83 and 84 are classified as the low-risk HPVs (6). HPV16 and 18 are the most common types, accounting for ~70% of cervical cancers around the world (7).…”

Section: Introductionmentioning

confidence: 99%

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

et al. 2015

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Abstract. Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4 + /CD8 + T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

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“…After the integration, although the L1 gene is intact in the integrated HPV genome, the startup sequence needed for L1 normal transcription undergoes rearrangement from upstream to downstream of L1 gene. Consequently, the transcription of the L1 gene cannot start, thus there is no L1 expression [ 11 – 16 ]. Based on the above-mentioned reasons, it is widely believed by researchers in the field of HPV-associated tumors that there is no L1 protein expression in HPV induced tumors [ 9 – 13 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, the transcription of the L1 gene cannot start, thus there is no L1 expression [ 11 – 16 ]. Based on the above-mentioned reasons, it is widely believed by researchers in the field of HPV-associated tumors that there is no L1 protein expression in HPV induced tumors [ 9 – 13 , 16 ]. But the question arises as to whether the above viewpoint really true?…”

Section: Introductionmentioning

confidence: 99%

Observations on the expression of human papillomavirus major capsid protein in HeLa cells

Changyi

et al. 2015

Cancer Cell Int

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BackgroundThe goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells.MethodsHPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control.ResultsHPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80–85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells.ConclusionsThe inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

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Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

Cited by 16 publications

References 32 publications

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

Observations on the expression of human papillomavirus major capsid protein in HeLa cells

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