scholarly journals The Expression of Oct3/4A mRNA and Not Its Isoforms is Upregulated by the HPV16 E7 Oncoprotein

Author(s):  
Yazmín Gómez-Gómez ◽  
Jorge Organista-Nava ◽  
Sayuri Itzel Clemente-Periván ◽  
Alfredo Lagunas-Martinez ◽  
Eric Genaro Salmerón-Bárcenas ◽  
...  

Abstract Oct3/4 a transcription factor is involved in maintaining the characteristics of cancer stem cells. Oct3/4 can be expressed differentially with respect to the progression of CC. In addition, Oct3/4 can give rise to three isoforms by alternative splicing of the mRNA Oct3/4A, Oct3/4B and Oct3/4B1. The aim of this study was to evaluate the mRNA expression from Oct3/4A, Oct3/4B and Oct3/4B1 in low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC) samples, and measure the effect of the HPV16 E7 oncoprotein on the mRNA expression from Oct3/4 isoforms in the C-33 A cell line. The expression levels of Oct3/4A, Oct3/4B and Oct3/4B1 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with LSILs, HSILs and CC. Additionally, C-33 A cells that expressed the HPV16 E7 oncoprotein were established to evaluate the effect of E7 on the expression of Oct3/4 mRNA isoforms. Oct3/4A (p=0.02), Oct3/4B (p=0. 001) and Oct3/4B1 (p<0. 0001) expression is significantly higher in patients with LSIL, HSIL and CC than in woman with non-IL. In the C-33 A cell line, the expression of Oct3/4A mRNA in the presence of the E7 oncoprotein increased compared to that in nontransfected C-33 A cells. Oct3/4B and Oct3/4B1 mRNA were expressed at similar levels among the different groups. These data indicate that only the mRNA of Oct3/4A is upregulated by the HPV16 E7 oncoprotein.

2020 ◽  
Vol 16 (1) ◽  
pp. 18-22
Author(s):  
Eronmwon E. Gbinigie ◽  
Joshua Fogel ◽  
Maggie Tetrokalashvili

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bei Zhang ◽  
Shuhui Hong ◽  
Guihui Zhang ◽  
Fengnian Rong

Abstract Background Colposcopy offers an accurate way to the diagnose of cervical precancerous lesions. However, the diagnostic accuracy of colposcopy is unsatisfied. This study was to evaluate colposcopic accuracy according to the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) terminology. Methods A retrospective cohort study was performed in 1,838 patients who underwent colposcopy in Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University from October 2013 to April 2018. Using conization or cervical biopsy pathology as the gold standard, the agreement between colposcopic diagnosis and pathologic diagnosis was calculated, and correlations between variables were analyzed. Results As an authoritative and widely used terminology for colposcopy diagnosis, the 2011 IFCPC terminology has certain clinical practicality and diagnostic accuracy. However, some signs such as mosaic, punctation, sharp border, inner border sign and ridge sign had high specificity but unsatisfactory sensitivity, which limited the diagnostic value. Therefore, we discussed the Lugol’s staining, a very common sign in colposcopy, and analyzed the diagnostic significance of bright yellow staining in low-grade squamous intraepithelial lesion (LSIL) and mustard yellow staining in high-grade squamous intraepithelial lesion (HSIL). The results showed that mustard yellow may be a valuable indicator in the diagnosis of HSIL. Conclusion The 2011 IFCPC colposcope terminology has standardized interpretations of the colposcopic findings and improved the accuracy of colposcopy diagnosis. The aceto-white epithelium still has important diagnostic value; however, the value of a few signs is needed to be discussed and new signs are expected to be discovered. Although the significance of Lugol’s staining was diminishing, mustard yellow might be a valuable indicator for the diagnosis of HSIL.


2008 ◽  
Vol 132 (8) ◽  
pp. 1290-1294 ◽  
Author(s):  
Ann T. Moriarty ◽  
Mary R. Schwartz ◽  
Galen Eversole ◽  
Marilee Means ◽  
Amy Clayton ◽  
...  

Abstract Context.—Oncogenic, high-risk human papillomavirus (HR-HPV) testing is used to evaluate women who are older than 20 years with atypical squamous cells of undetermined significance (ASC-US) and in conjunction with a screening Papanicolaou test in women older than 30 years. Objectives.—To evaluate the 2006 laboratory practice data from laboratories incorporating human papillomavirus (HPV) testing with the Papanicolaou test. Design.—To use the College of American Pathologists (CAP) Supplemental Questionnaire Survey for 2006 to determine laboratory practices of participants in the CAP Interlaboratory Comparison Program in Cervicovaginal Cytology. Results.—A total of 679 laboratories responded to the questionnaire. Most (73%) refer HPV testing to reference laboratories. Nine percent perform HPV testing in cytology. Forty-five percent offer low-risk HPV (LR-HPV) testing. The most common reflex is ASC-US, although HR-HPV is also offered with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or any other Papanicolaou test result. Digene Hybrid Capture II is the most common method. Human papilloma virus median test volumes are 55 monthly. Frequency distributions of HPV test volumes are significantly different from those found in 2003. Laboratories performing in-house testing reported significantly higher monthly HPV volumes (P &lt; .001). Median rates for HR-HPV positivity are 36.6% for ASC-US, 50.0% for atypical squamous cells, cannot exclude HSIL (ASC-H), and 4% for women 30 years of age and older in conjunction with a screening Papanicolaou test. Conclusions.—Reference HPV testing remains the most common pattern. The most common reflex indication is for ASC-US, but HPV testing is modified locally to include a variety of scenarios. LR-HPV testing is commonly offered despite its lack of clinical significance. These data form a baseline for ongoing monitoring of HPV testing practice trends.


2018 ◽  
Vol 143 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Barbara A. Crothers ◽  
Mohiedean Ghofrani ◽  
Chengquan Zhao ◽  
Leslie G. Dodd ◽  
Kelly Goodrich ◽  
...  

Context.— Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. Objective.— To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. Design.— We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. Results.— There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL (P &lt; .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). Conclusions.— More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.


2020 ◽  
Vol 3 (2) ◽  
pp. 392-394
Author(s):  
Alina Karna ◽  
Nisha Sharma

Adenoid basal carcinoma of the uterine cervix is a rare low-grade tumor and its cell origin is still obscure. Adenoid basal carcinoma can be confused with adenoid basal hyperplasia, adenoid cystic carcinoma, and basaloid squamous cell carcinoma of the cervix. We present here a case of a 59 year-old-female who initially presented with a high-grade squamous intraepithelial lesion on Pap smear. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology revealed focal invasive adenoid basal carcinoma with extensive areas of a high-grade squamous intraepithelial lesion involving the endocervical gland. The immunohistochemical stain was positive for p16.


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