Figure 2 - uploaded by Anne Fortino Rositch
Content may be subject to copyright.
High-grade squamous intraepithelial lesion (HSIL/CIN 2). (b) Absent expression of L1; L2 showed similar findings (not shown). (c) High-grade squamous intraepithelial lesion (HSIL/CIN 3). (d) The lesion lacks expression of L1; L2 expression was absent as well (not shown).
Source publication
While cervical cancer screening relies on cervical cytology and high-risk HPV detection, histologic diagnosis, and specifically lesion grade, is the main parameter that drives clinical management of screen-positive women. Morphologically diagnosed squamous intraepithelial lesions (SIL/CIN) regress spontaneously in more than half of the cases, but i...
Similar publications
This study originally aimed to investigate whether the overexpression of SOX2 is associated with the poor prognosis of patients with squamous cell carcinoma of the esophagus. However, we unexpectedly found that esophageal squamous cell carcinomas completely lacking SOX2 expression showed distinct pathologic features and highly aggressive clinical c...
CD200, a marker currently utilized in the diagnosis of B-cell lymphoma, is uniformly positive in chronic lymphocytic leukemia/chronic lymphocytic leukemia, and is usually absent in mantle cell lymphoma. Over a 6 year-period, of 668 mantle cell lymphoma assessed by flow cytometry, CD200 expression was detected in 25 patients (~4%). All 25 patients h...
The assessment of human epidermal growth factor receptor 2 (HER2) status in gastric cancer is crucial in selecting patients who may benefit from targeted therapy, yet heterogeneous expression could represent an important drawback for HER2 testing. We aimed to analyze (i) HER2 heterogeneity in primary gastric cancers, pre-neoplastic and metastatic l...
Combination antiretroviral therapy is highly effective in HIV infection, leading to decreased incidences of AIDS-defining neoplasms. However, HIV patients still have a 10-fold increased risk of developing classical Hodgkin lymphoma compared with the general population. As Hodgkin- and Reed-Sternberg cells represent only a minority in the tumor infi...
ERBB2 (HER-2/neu) amplification and/or overexpression are associated with poor prognosis in node-positive breast carcinoma. Its prognostic value in node-negative cases and its predictive value for response to chemotherapy remain controversial. This may be related to the use of molecular methods, which are sensitive to dilution of tumor material by...
Citations
... (26,27,49) It has been reported that during normal life cycle, the highly immunogenic L1/L2 proteins were not detected in undifferentiated basal cells, however, they were detected in differentiated superficial cells. (50) During viral life cycle, L1/L2 genes were highly methylated in undifferentiated basal cells but become unmethylated in differentiated cells leading to the expression of viral late proteins necessary for viral particle production in the upper part of the epithelium. (51) HPV late promoter was active and activated due to expression of cellular proteins such as cyclin dependent kinase 8 (CDK8) and CDK9 in differentiated cells. ...
... Productive viral infection is characterized by genome amplification and expression of late viral genes responsible for virion assembly, notably the capsid proteins. This late gene expression is restricted to terminallydifferentiated, superficial squamous epithelial cells [6] . ...
... Overall the preinvasive lesions showed significant increased expression of L1 than invasive lesions. Our study findings corroborates with the previous studies, where declining L1 positivity with higher grade of lesions found, though the positivity rates differs in different studies [6], [11], [12], [13] . ...
... 4 There has been great interest in using adjunctive biomarkers to improve the classification and reliability of histopathologic diagnoses, based on H&E staining, of cervical abnormalities, especially to reduce the overdiagnosis of CIN2 on H&E and clarify the clinical significance of CIN2 (ie, distinguish between benign CIN2 diagnoses potentially destined to regress or not progress from CIN2 diagnoses that reflect the presence of high-grade cervical abnormalities that for safety should be treated to reduce the risk of cancer development). Some of the biomarkers that have been investigated for clarifying the meaning of an H&E diagnosis of CIN2 on biopsy include (but are not limited to) HPV16, 15 HPV L1, 16,17 Ki-67, 7,16 E4, 18,19 and p16 INK4a (p16) 7,11,16 detection. ...
Context.—
Lower Anogenital Squamous Terminology (LAST) standardization recommended p16 INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs).
Objective.—
To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.
Design.—
A statewide, stratified sample of cervical biopsies diagnosed by the community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.
Results.—
Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall ( P trend ≤ .001) and within each HPV risk group ( P trend ≤ .001 except for low-risk HPV [ P trend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group ( P trend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies ( P < .001). p16 IHC–positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL ⁺ cytology, or to be diagnosed as CIN3 ⁺ by the EP ( P < .001 for all). p16 IHC–positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC–negative, CP-diagnosed CIN2 biopsies ( P < .001).
Conclusions.—
p16 IHC–positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of “HSIL” diagnosis, which includes p16 IHC–positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.
... The increased sensitivity of cell blocks in the diagnosis of malignant conditions of cervix may be due to better preservation of cytomorphologic features (like cell balls, papillae and three dimentional cluster), better staining characteristics of the nucleus, nucleoli, and cytoplasm, clear recognition of nuclear and cytoplasmic features. The tissue fragments can easily be interpreted in a biopsy-like fashion [15,17]. In the present study, one case which was diagnosed as HSIL turned out to be SCC in cell blocks and a case of inflammatory smear in pap was reported as dysplasia in cell blocks. ...
Background: Cervical cancer is the second most common cancer among women worldwide and leading causes of cancer deaths amongst women. Cell blocks prepared from liquid-based specimens can serve as a useful adjunct and cell blocks can be further subjected for ancillary molecular techniques. Materials and Methods: In the present study 60 cell blocks were prepared from Manual liquid-basedcytology (MLBC) specimen collected in liquid fixative. Results were compared with cytology smears and histopathological correlation was obtained in 19 cases. P16 and Ki67 were used whenever required. Results: In the present study out of 60 cases of cell blocks 10 cases had no deposit. Of the other 50 cases, 7 cases (14%) were neoplastic and 43(86%) were non-neoplastic. The sensitivity and specificity of cell block, LBC and CPS were 75% and 93%, 66% and 84%, 50% and 70% respectively for neoplastic lesions of cervix. Concordance Rate of CB/Histopathology Vs CPS/Histopathology is 74% vs. 54%. Ki 67 and p16INK4a were used whenever sample was sufficient. Conclusion: In the present study we found that cell blocks prepared from the LBC specimens aid in the diagnosis of neoplastic lesions of cervix and are particularly valuable in distinguishing carcinoma cervix from intraepithelial lesions. Cell blocks can be further subjected to ancillary tools like immunohistochemistry and HPV- DNA testing.
... Therefore, the presence of HPV proteins provides critical evidence for a risk of cervical cancer. The expression of the HPV E7 oncoprotein mainly starts in the basal layer cells of the cervical squamous epithelium and is maintained in the superficial layer (Litjens et al. 2013), and HPV L1 is mainly expressed in the superficial layer (Yemelyanova et al. 2013). Therefore, it is thought that the superficial layer cells may reflect the cancerous state of the cervix. ...
... HPV L1 is expressed during the maturation of basal cells into the superficial layer cells of cervix tissue, and may therefore be mainly found in the superficial layer (Yemelyanova et al. 2013;Lee et al. 2014). One study suggested that HPV L1 is located in the cytoplasm as well as the nuclei of cells of the superficial cervix tissue in cervical cancers (Lee et al. 2008), and others found that HPV was mainly located in the cytoplasm of the superficial layer cells in cervical cancer patients (Hernandez et al. 2011). ...
There has been no attempt to apply protein-based markers of exfoliated cervical cells (ECCs) for primary screening of cervical cancer. In the present study, the levels of six tumor-associated protein [TAPs: Sialyl Lewis A (SLeA), Cancer Antigen 15-3 (CA 15-3), p53, heat shock protein (Hsp)70, Hsp27 and squamous cervical carcinoma antigen (SCCA)]and of two human papillomavirus (HPV) viral proteins (HPV16 E7 and HPV16 L1) of ECCs lysates were evaluated by enzyme-linked immunosorbent assays (ELISAs).The wells of 96-well plates were coated with the ECCs lysates from normal, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cancer groups, and candidate proteins were detected by relevant antibodies. SLeA level decreased with increasing severity of lesions, whereas the levels of other candidate proteins increased. SLeA, HPV16 L1 and p53 levels appeared more useful for detecting cervical lesions than the other candidates. The combination of ELISA-SLeA and ELISA-HPV16 L1 could efficiently detect cervical lesions from normal. The combination of ELISA-SLeA and ELISA-p53 could powerfully discriminate cancer from normal with 91.3% sensitivity and 96.7% specificity. The protein levels of ECCs have great potential as biomarkers for primary screening of cervical cancer.
... In concordance with our results, Khan et al. [15] reported that HPV type 16 was significantly associated with a higher incidence of CIN3 in LSIL. Various biomarkers were developed to reduce the discrepancy between cervical cytology and pathology and identify patients at the risk of developing higher grade pathology ( Table 2) [6,[8][9][10][16][17][18][19][20][21][22]. ...
... Chen et al. [18] 75 HPV L1, p16, Ki-67 CIN 1-3 HPV L1 negativity was related with high-grade CIN. Negri et al. [19] 66 HPV L1, p16 CIN1, CIN3 HPV L1 negativity and p16 positivity shows poor prognosis Yemelyanova et al. [20] 212 HPV L1, L2 CIN1-3 HPV L1 and L2 negativity are found more frequently in high grade CIN. HPV genome PCR Cricca et al. [6] 166 HPV E2/E6 ratio CIN1-3, Cancer No full integration status is found in CIN1 and no episomal status is found in cancer. ...
Objective:
Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ≥cervical intraepithelial neoplasia (CIN) 2 lesions.
Methods:
Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1-3 and squamous cell carcinoma [SCC]) to evaluate the association.
Results:
The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p<0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p<0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p<0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793-0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562-0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826-0.917) for the prediction of ≥CIN2 lesions.
Conclusion:
To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis.
... CLUSTAL W (1.81) multiple sequence alignments of the amino acid residues in the E6 protein sequences among high-risk HPV types cause cervical cancer. Four high-risk genotypes was identified;16,18,31,45. Columns indicate identical amino acids in the same position in all types analyzed are exclusively indicated by an asterisk (*) which showed fully conserved residues, whereas alignments showing the presence of similar amino acids are represented by other symbols (:) for conservation of strong groups or (.) for conservation of weak groups. ...
Human Papillomavirus (HPV) is a standout amongst the most commonly reported over 100 types, among them genotypes 16, 18, 31 and 45 are the high-risk HPV. Herein, we designed the oligonucleotide probe for the detection of predominant HPV type 16 for the sensing applications. Conserved amino acid sequences within E6 region of the open reading frame in the HPV genome was used as the basis to design oligonucleotide probe to detect cervical cancer. Analyses of E6 amino acid sequences from the high-risk HPVs were done to check the percentage of similarity and consensus regions that cause different cancers, including cervical cancer. Basic local alignment search tools (BLAST) have given extra statistical parameters, for example, desire values (E-values) and score bits. The probe, 'GGG GTC GGT GGA CCG GTC GAT GTA' was designed with 66.7% GC content. This oligonucleotide probe is designed with the length of 24 mer, GC percent is between 40 and 70, and the melting point (Tm) is above 50°C. The probe needed an acceptable length between 22 and 31 mers. The choice of region is identified here can be used as a probe, has implications for HPV detection techniques in biosensor especially for clinical determination of cervical cancer.
... Although this antibody was able to detect various PV including HPV-1, 6, 11, 16, 18, and 31, its reactivity with all types has not been determined. In addition, L1 capsid proteins are not expressed in all papilloma associated lesions, explaining possible false negative results (Yemelyanova et al., 2013). Papillomaviruses are an established cause of skin disease in dogs. ...
Background
Corns are hard protuberances that occur on the digital footpads of Greyhound dogs. The cause of these lesions is unknown and there is little information about them in the veterinary literature. We received anecdotal examples of dog to dog spread of corns suggesting an infectious cause. The aim of this study was to determine if papillomavirus (PV) is associated with Greyhound corns.
Methods
We examined four corns from two unrelated adult Greyhound dogs that resided in Florida and Washington, respectively, for PV by PCR. The samples were obtained by owner coring of two lesions from one dog and laser removal of two lesions from the other dog. Total nucleic acid was extracted and DNA was amplified using two PCR primer sets that have been shown to amplify a broad range of PVs from humans and animals: FAP59/ FAP64 and MY11/ MY09. The DNA sequences were compared with all sequences in GenBank. Formalin-fixed, paraffin-embedded tissue from the footpads of four dogs with other inflammatory dermatoses were also examined.
Results
PV DNA was amplified from all four corn lesions, while no PV DNA was amplified from other tissues. Comparison of the 444-bp sequences amplified by the MY11/ MY09 primers identified two different PVs. One showed 96% nucleotide sequence similarity with the L1 gene of canine PV type 12. The other showed 78% similarity to canine PV type 16 and, therefore, represents a novel PV. In one of the corns, infection by two of the identified PVs was found.
Discussion
These results suggest PV infection could be involved in the pathogenesis of corns in Greyhound dogs.
... Although this antibody was able to detect various PV including 144 HPV-1, 6, 11, 16, 18, and 31, its reactivity with all types has not been determined. In addition, 145 L1 capsid proteins are not expressed in all papilloma associated lesions, explaining possible false 146 negative results (Yemelyanova et al, 2013). 147 Papillomaviruses are an established cause of skin disease in dogs. ...
Background – Corns are hard protuberances that occur on the digital footpads of Greyhound dogs. The cause of these lesions is unknown and there is little information about them in the veterinary literature. We received anecdotal examples of dog to dog spread of corns suggesting an infectious cause. The aim of this study was to determine if papillomavirus (PV) is associated with Greyhound corns. Methods – We examined four corns from two unrelated adult Greyhound dogs that resided in Florida and Washington, respectively, for PV by PCR. The samples were obtained by owner coring of two lesions from one dog and laser removal of two lesions from the other dog. Total nucleic acid was extracted and DNA was amplified using two PCR primer sets that have been shown to amplify a broad range of PVs from humans and animals: FAP59/ FAP64 and MY11/ MY09. The DNA sequences were compared with all sequences in GenBank. Formalin-fixed, paraffin-embedded tissue from the footpads of four dogs with other inflammatory dermatoses were also examined. Results – PV DNA was amplified from all four corn lesions, while no PV DNA was amplified from other tissues. Comparison of the 300-400-bp sequences amplified by the MY11/ MY09 primers identified two different PVs. One showed 96% nucleotide sequence homology with the L1 gene of canine PV type 12. The other showed 78% homology to canine PV type 16, and, therefore, represents a novel PV. In one of the corns, infection by two of the identified PVs was found. Discussion – These results suggest PV infection could be involved in the pathogenesis of corns in Greyhound dogs.
... Although this antibody was able to detect various PV including 144 HPV-1, 6, 11, 16, 18, and 31, its reactivity with all types has not been determined. In addition, 145 L1 capsid proteins are not expressed in all papilloma associated lesions, explaining possible false 146 negative results (Yemelyanova et al, 2013). 147 Papillomaviruses are an established cause of skin disease in dogs. ...
Background – Corns are hard protuberances that occur on the digital footpads of Greyhound dogs. The cause of these lesions is unknown and there is little information about them in the veterinary literature. We received anecdotal examples of dog to dog spread of corns suggesting an infectious cause. The aim of this study was to determine if papillomavirus (PV) is associated with Greyhound corns. Methods – We examined four corns from two unrelated adult Greyhound dogs that resided in Florida and Washington, respectively, for PV by PCR. The samples were obtained by owner coring of two lesions from one dog and laser removal of two lesions from the other dog. Total nucleic acid was extracted and DNA was amplified using two PCR primer sets that have been shown to amplify a broad range of PVs from humans and animals: FAP59/ FAP64 and MY11/ MY09. The DNA sequences were compared with all sequences in GenBank. Formalin-fixed, paraffin-embedded tissue from the footpads of four dogs with other inflammatory dermatoses were also examined. Results – PV DNA was amplified from all four corn lesions, while no PV DNA was amplified from other tissues. Comparison of the 300-400-bp sequences amplified by the MY11/ MY09 primers identified two different PVs. One showed 96% nucleotide sequence homology with the L1 gene of canine PV type 12. The other showed 78% homology to canine PV type 16, and, therefore, represents a novel PV. In one of the corns, infection by two of the identified PVs was found. Discussion – These results suggest PV infection could be involved in the pathogenesis of corns in Greyhound dogs.
