Detection of human papillomavirus type 16 early-gene transcription by reverse transcription-PCR is associated with abnormal cervical cytology.

ABSTRACT Essential to the oncogenic properties of human papillomavirus type 16 (HPV-16) are the activities encoded by the early gene product E7. HPV-16 E7 (E7.16) binds to cellular factors involved in cell cycle regulation and differentiation. These include the retinoblastoma tumor suppressor protein (Rb) and histone deacetylase (HDAC) complexes. While the biological significance of these interactions remains unclear, E7 is believed to help maintain cells in a proliferative state, thus establishing an environment that is conducive to viral replication. Most pathways that govern cell growth converge on downstream effectors. Among these is the cdc25A tyrosine phosphatase. cdc25A is required for G1/S transition, and its deregulation is associated with carcinogenesis. Considering the importance of cdc25A in cell cycle progression, it represents a relevant target for viral oncoproteins. Accordingly, the present study focuses on the putative deregulation of cdc25A by E7.16. Our results indicate that E7.16 can impede growth arrest induced during serum starvation and keratinocyte differentiation. Importantly, these E7-specific phenotypes correlate with elevated cdc25A steady-state levels. Reporter assays performed with NIH 3T3 cell lines and human keratinocytes indicate that E7 can transactivate the cdc25A promoter. In addition, transcriptional activation by E7.16 requires the distal E2F site within the cdc25A promoter. We further demonstrate that the ability of E7 to abrogate cell cycle arrest, activate cdc25A transcription, and increase cdc25A protein levels requires intact Rb and HDAC-1 binding domains. Finally, by using the cdk inhibitor roscovitine, we reveal that E7 activates the cdc25A promoter independently of cell cycle progression and cdk activity. Consequently, we propose that E7.16 can directly target cdc25A transcription and maintains cdc25A gene expression by disrupting Rb/E2F/HDAC-1 repressor complexes.

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Characteristics of high-risk human papillomavirus infection in women with abnormal cervical cytology: a population-based study in Shanxi Province, China

10.21203/rs.2.15784/v1 ◽

2019 ◽

Author(s):

Li Song ◽

Yuanjing Lyu ◽

Ling Ding ◽

Xiaoxue Li ◽

Wen Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Hpv Infection ◽

Cervical Cytology ◽

Shanxi Province ◽

Low Grade ◽

Squamous Intraepithelial Lesion ◽

Abnormal Cervical Cytology ◽

Intraepithelial Lesion

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.

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Relationships of Sexually Transmitted Infections, Bacterial (STI) with High-Risk Human Papillomavirus (HR-HPV) and Abnormal Cervical Cytology in Gynecological Outpatients

Journal of the American Society of Cytopathology ◽

10.1016/j.jasc.2015.09.080 ◽

2015 ◽

Vol 4 (6) ◽

pp. S34

Author(s):

Sung Ran Hong ◽

Tae Jin Kim ◽

In Ho Lee ◽

Hye Sun Kim

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Sexually Transmitted Infections ◽

Cervical Cytology ◽

Sexually Transmitted ◽

Abnormal Cervical Cytology

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Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait

Archives of Virology ◽

10.1007/s00705-013-1658-y ◽

2013 ◽

Vol 158 (8) ◽

pp. 1687-1699 ◽

Cited By ~ 3

Author(s):

Rana Al-Awadhi ◽

Wassim Chehadeh ◽

Waleed Al-Jassar ◽

Jehad Al-Harmi ◽

Eyad Al-Saleh ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Human Papillomavirus ◽

Cervical Cytology ◽

Abnormal Cervical Cytology

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Contribution of human papillomavirus (HPV) genotypes to persistently abnormal cervical cytology in a high-risk Latino population

Gynecologic Oncology ◽

10.1016/j.ygyno.2014.03.442 ◽

2014 ◽

Vol 133 ◽

pp. 167-168

Author(s):

Y.A. Lyons ◽

A.A. Kamat ◽

M.R. Schwartz ◽

D.R. Mody ◽

H. Zhou ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Cervical Cytology ◽

Latino Population ◽

Abnormal Cervical Cytology ◽

Hpv Genotypes

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Risk Factors for Human Papillomavirus Infection and Abnormal Cervical Cytology Among Perinatally Human Immunodeficiency Virus-Infected and Uninfected Asian Youth

Clinical Infectious Diseases ◽

10.1093/cid/ciy144 ◽

2018 ◽

Vol 67 (4) ◽

pp. 606-613 ◽

Cited By ~ 8

Author(s):

Annette H Sohn ◽

Stephen J Kerr ◽

Rawiwan Hansudewechakul ◽

Sivaporn Gatechompol ◽

Kulkanya Chokephaibulkit ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Cervical Cytology ◽

Low Grade ◽

Sexually Transmitted ◽

Screening Programs ◽

Perinatal Hiv ◽

Abnormal Cervical Cytology ◽

Immunodeficiency Virus

AbstractBackgroundInfection with high-risk human papillomavirus (HR-HPV) may be higher in perinatally human immunodeficiency virus (HIV)–infected (PHIV) than HIV-uninfected (HU) adolescents because of long-standing immune deficiency.MethodsPHIV and HU females aged 12–24 years in Thailand and Vietnam were matched by age group and lifetime sexual partners. At enrollment, blood, cervical, vaginal, anal, and oral samples were obtained for HPV-related testing. The Wilcoxon and Fisher exact tests were used for univariate and logistic regression for multivariate analyses.ResultsNinety-three PHIV and 99 HU adolescents (median age 19 [18–20] years) were enrolled (June 2013–July 2015). Among PHIV, 94% were currently receiving antiretroviral therapy, median CD4 count was 593 (392–808) cells/mm3, and 62% had a viral load <40 copies/mL. Across anogenital compartments, PHIV had higher rates of any HPV detected (80% vs 60%; P = .003) and any HR-HPV (60% vs 43%, P = .02). Higher proportions of PHIV had abnormal Pap smears (eg, atypical squamous cells of unknown significance [ASC-US], 12% vs 14%; low-grade squamous intraepithelial neoplastic lesions, 19% vs 1%). After adjusting for ever being pregnant and asymptomatic sexually transmitted infections (STI) at enrollment, PHIV were more likely to have HR-HPV than HU (odds ratio, 2.02; 95% confidence interval, 1.09–3.77; P = .03).ConclusionsPerinatal HIV infection was associated with a higher risk of HR-HPV and abnormal cervical cytology. Our results underscore the need for HPV vaccination for PHIV adolescents and for prevention and screening programs for HPV and other STIs.

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