Differential expression of p53 and p21 in low grade cervical squamous intraepithelial lesions infected with low, intermediate, and high risk human papillomaviruses

Cancer ◽  
2000 ◽  
Vol 89 (6) ◽  
pp. 1300-1307 ◽  
Author(s):  
Athina Giannoudis ◽  
C. Simon Herrington
Keyword(s):  
High Risk ◽  
Differential Expression ◽  
Human Papillomaviruses ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cervical Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions

Relevance of the Pap Test: A Report of HPV-DNA Test-Negative High-Grade Squamous Intraepithelial Lesions of the Female Lower Genital Tract

2016 ◽  
Vol 60 (5) ◽  
pp. 445-450 ◽  
Author(s):  
Yiang Hui ◽  
Katrine Hansen ◽  
Jayasimha Murthy ◽  
Danielle Chau ◽  
C. James Sung ◽  
...  
Keyword(s):  
High Risk ◽  
Pap Test ◽  
Human Papillomaviruses ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cytologic Examination ◽  
Dna Test ◽  
Hpv Dna ◽  
Intraepithelial Lesions ◽  
Hpv Dna Test

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.

scholarly journals Colposcopy, cervical cytology and human papillomavirus detection as screening tools for cervical cancer

2001 ◽  
Vol 7 (1-2) ◽  
pp. 100-105
Author(s):  
Al Alwan Al Alwan
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Pap Test ◽  
Screening Tools ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Sampling Device ◽  
Squamous Cells ◽  
The Bethesda System ◽  
Intraepithelial Lesions

A cohort of 77 women referred for routine screening or investigation of Pap test abnormality underwent colposcopic examination. Pap-stained liquid-based preparations were diagnosed and categorized according to the Bethesda system. Residual material on the sampling device was used to detect high-risk oncogenic human papillomavirus DNA. Although the colposcopic failure rate was higher than that of cytology, no lesion was missed when both methods were used together. High-risk types were recorded in 24% of patients with atypical squamous cells of undetermined significance, 45% with low-grade squamous intraepithelial lesions and 79% with high-grade squamous intraepithelial lesions-indicating that the efficacy of cytological screening can be improved by papillomavirus detection.

scholarly journals Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis

2003 ◽  
Vol 121 (3) ◽  
pp. 128-132 ◽  
Author(s):  
Sylvia Michelina Fernandes Brenna ◽  
Kari Juhani Syrjänen
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cell Cycle Checkpoints ◽  
Low Grade ◽  
Clinical Progression ◽  
Squamous Intraepithelial Lesions ◽  
High Risk Hpv ◽  
Intraepithelial Lesions

The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.

scholarly journals Use of high-risk human papillomavirus testing in patients with low-grade squamous intraepithelial lesions

2011 ◽  
Vol 119 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Angelique W. Levi ◽  
Malini Harigopal ◽  
Pei Hui ◽  
Kevin Schofield ◽  
David C. Chhieng
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Human Papillomavirus Testing ◽  
Intraepithelial Lesions

scholarly journals Detection of antibodies against a human papillomavirus (HPV) type 16 peptide that differentiate high-risk from low-risk HPV-associated low-grade squamous intraepithelial lesions

2004 ◽  
Vol 85 (9) ◽  
pp. 2643-2650 ◽  
Author(s):  
Leticia Rocha-Zavaleta ◽  
Juana P. Ambrosio ◽  
Maria de Lourdes Mora-Garcia ◽  
Fernando Cruz-Talonia ◽  
Jorge Hernandez-Montes ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Cancer Patients ◽  
Low Risk ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Hpv Dna ◽  
Iga Antibodies ◽  
High Risk Hpv ◽  
Intraepithelial Lesions

A nonapeptide (16L1) was derived from the human papillomavirus type 16 (HPV-16) major capsid protein and tested for detection of potential cross-reactive serum IgG and cervical IgA antibodies in low- and high-risk HPV-associated low-grade squamous intraepithelial lesions (LSIL) and cervical cancer patients by ELISA. The IgG response was similar in women with low-risk HPV-associated LSIL and controls (P=0·1). In contrast, more than 90 % of patients with high-risk HPV-associated LSIL were seropositive. Although tumours from cancer patients were all positive for the presence of high-risk HPV DNA, the level of seropositivity decreased significantly in this group (P<0·0001). Cervical IgA antibodies were also detected in a significantly high proportion of women with high-risk HPV-associated LSIL compared with controls. However, the proportion of IgA-positive patients was lower than the proportion of IgG seropositives. In conclusion, the 16L1 peptide appears to be a high-risk type-common epitope that induces cross-reactive antibodies in high-risk, but not low-risk, HPV-associated LSIL patients, allowing differentiation of high- and low-risk infected women at this stage of infection.

Patterns of Cytokeratin 7 Expression in Cervical Squamous Intraepithelial Lesions

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S37-S37
Author(s):  
M Youssef ◽  
S Canete-Portillo ◽  
A Yemelyanova ◽  
B Ronnett
Keyword(s):  
Significant Variation ◽  
Significant Proportion ◽  
Immunohistochemical Analysis ◽  
Low Grade ◽  
Full Thickness ◽  
Cytokeratin 7 ◽  
Squamous Intraepithelial Lesions ◽  
Squamocolumnar Junction ◽  
Cervical Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions

Abstract Introduction/Objective It has been suggested that cervical high-grade squamous intraepithelial lesions (HSIL/CIN2-3) arise from squamocolumnar junction cells that express cytokeratin 7 (CK7). Significant CK7 expression (gradation or full-thickness) has been proposed as a marker of progression of low-grade squamous intraepithelial lesions (LSIL/CIN1) to HSIL and of persistence of HSIL/CIN2. The goal of the study is to survey patterns of CK 7 expression in the different grades of squamous intraepithelial lesions (SILs). Methods 65 cervical specimens (biopsies and excisions) containing 95 lesions of different grades were assessed by immunohistochemical analysis (IHC) for CK7 expression. 26 cases contained more one lesion grade. The diagnosis of HSIL (CIN2-3) was confirmed by p16 IHC. CK7 expression was scored negative, patchy, gradation (i.e., top-down), or full-thickness pattern. In cases with heterogeneous staining, the strongest pattern was used for analysis. Results There was significant variation in patterns within morphologically contiguous lesional foci; staining heterogeneity was noted in 42% of cases. All patterns of expression were encountered in all lesion grades. LSIL/CIN1 (n=47), either alone (n=27) or in combination with HSIL (n=20), often lacked CK7 expression (53%) or were patchy (17%). The frequency of significant (gradation or full-thickness) CK7 expression in LSIL with concomitant HSIL was greater than LSIL occurring alone (40% vs. 22%, respectively). HSIL/CIN3 (n=19) was dominated by full-thickness expression (57%). HSIL/CIN2 (n=29) had a very heterogeneous spectrum of expression with 34% of cases lacking expression. Conclusion CK7 expression is variable across all grades of SILs. LSIL with concomitant HSIL was associated with significant CK7 expression more frequently than LSIL alone. Significant proportion of HSIL, particularly CIN2, lacks CK7 expression. Given this variability, caution is advised regarding the use of CK7 expression as a marker of progression.

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