A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine

ABSTRACT: Introduction: Human papillomavirus (HPV) is considered a necessary causative agent for developing oropharyngeal, anal and cervical cancer. Among women in Ecuadorian population, cervical cancer ranks as the second most common gynecological cancer. Not many studies about HPV burden have been published in Ecuador, and genotypes distribution has not been established yet. The little data available suggest the presence of other genotypes different than 16 and 18. Objectives: In the present study, we attempt to estimate the prevalence of HPV 16, HPV 18 and other 35 genotypes among Ecuadorian women undergoing cervical cancer screening. The overall prevalence of HPV infection was also estimated. Methods: Routine cervical samples were analyzed using Linear Array(r) HPV Genotyping test (Roche). Results: A total of 1,581 cervical samples obtained from Ecuadorian women undergoing cervical cancer screening were included in this study. HPV DNA was detected in 689 cervical samples (43.58%). Of these samples, 604 (38.20%) were positive for a single HPV genotype, while another 85 (5.37%) samples were positive for multiple HPV types. Genotype 16 (5.50%) resulted in the most frequently detected type in both single and multiple infections. HPV 33 (4.55%) and HPV 11 (3.80%) occupied the second and the third place in frequency among all detected genotypes. Conclusions: Viral genotypes different from HPV 16 and HPV 18 are frequently detected among Ecuadorian women. The overall prevalence of HPV resulted higher than the one reported in other South American countries with a greater burden in the second and third decades of life.

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Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer

Case Reports in Obstetrics and Gynecology ◽

10.1155/2020/6806857 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Pablo Moreno-Acosta ◽

Alfredo Romero-Rojas ◽

Nicolas Vial ◽

Antonio Huertas ◽

Jinneth Acosta ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Invasive Cervical Cancer ◽

Transition Process ◽

Hpv Infection ◽

Low Grade ◽

Preneoplastic Lesions ◽

Hpv 16 ◽

Molecular Changes ◽

High Risk Hpv

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.

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Human Papillomavirus (Hpv) Typing in Relation to ras Oncogene mRNA Expression in HPV-Associated Human Squamous Cervical Neoplasia

The International Journal of Biological Markers ◽

10.1177/172460080502000409 ◽

2005 ◽

Vol 20 (4) ◽

pp. 257-263 ◽

Cited By ~ 5

Author(s):

I.N. Mammas ◽

A. Zafiropoulos ◽

S. Sifakis ◽

G. Sourvinos ◽

D.A. Spandidos

Keyword(s):

Cervical Cancer ◽

Polymerase Chain Reaction ◽

Human Papillomavirus ◽

Hpv Infection ◽

Cervical Neoplasia ◽

Chain Reaction ◽

Hpv 16 ◽

Expression Levels ◽

Hpv Typing ◽

Polymerase Chain

Objective Human papillomavirus (HPV) has been identified as the principal etiologic agent for cervical cancer and its precursors. Different HPV types have been associated with different oncogenic potential. The purpose of this study was to evaluate the relationship between specific HPV type infection and expression pattern of the ras family oncogenes in different grades of HPV-associated human cervical neoplasia. Methods HPV typing was performed using polymerase chain reaction (PCR) in 31 HPV-positive human cervical specimens from patients with squamous intraepithelial lesions (SIL) or squamous cervical carcinoma (SCC). The mRNA expression levels of H-, K- and N-ras oncogenes were examined using the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Statistical analyses were performed using SPSS software. Results Among patients with SCC, H-, K- and N-ras expression levels were higher in HPV 16/18-associated cases compared to HPV 16/18-unassociated samples (p=0.003, p=0.004 and p=0.0001, respectively). The expression levels for H-, K-and N-ras were significantly higher in SCC patients with multiple HPV infection compared with SCC patients with single HPV infection (p=0.009, p=0.01 and p=0.021, respectively). Among patients with SIL, no statistically significant relationship was found between ras expression and HPV status. Conclusion Our findings indicate the possible role of ras signaling interaction with “high-risk” HPV 16/18 and multiple HPV infection in cervical cancer development.

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TP53 Codon 72 Polymorphism does not Affect Risk of Cervical Cancer in Patients from the Gambia

The International Journal of Biological Markers ◽

10.1177/172460080301800405 ◽

2003 ◽

Vol 18 (4) ◽

pp. 280-283 ◽

Cited By ~ 7

Author(s):

G. Tanara ◽

C. Falugi ◽

A. Cesario ◽

S. Margaritora ◽

P. Russo ◽

...

Keyword(s):

Cervical Cancer ◽

Geographical Area ◽

Population Sample ◽

Hpv Infection ◽

The Gambia ◽

Control Group ◽

Genotype Distribution ◽

Hpv 16 ◽

Codon 72 ◽

Tp53 Polymorphism

Aims A case-control study was performed to investigate the relationship between cervical cancer and TP53 polymorphism at codon 72 in young black African women from The Gambia. Materials and Methods The TP53 polymorphism at codon 72 was examined by PCR amplification and SSCP analysis in 40 patients with primary cervical cancer and in 20 healthy women of the same age and from the same geographical area. The occurrence of TP53 polymorphism in combination with the HPV-16 E6 genotype (assayed by PCR) was evaluated. Results The distribution of TP53 genotypes in cervical cancer patients and in the control group was not statistically different (p=0.45) and homozygosity for argine at residue 72 was not associated with cervical cancer (odds ratio: 1.24; 95% confidence interval 0.21-9.16). Similarly, a different genotype distribution, cervical cancer and presence of HPV-16 E6 were not observed. Conclusions These results cannot rule out an association between TP53 polymorphism at codon 72, HPV infection and the etiology of cervical cancer in this population sample.

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State of HPV16 integration in Lithuanian women with cervical neoplasia

Open Medicine ◽

10.2478/s11536-011-0004-6 ◽

2011 ◽

Vol 6 (2) ◽

pp. 205-212

Author(s):

Agne Sepetiene ◽

Zivile Gudlevicienė ◽

Zana Bumbuliene ◽

Grazina Drasutiene ◽

Janina Didziapetriene

Keyword(s):

Cervical Cancer ◽

Hpv Infection ◽

Rapid Progression ◽

The European Union ◽

Cervical Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Cin Iii ◽

Cell Genome ◽

Virus Integration

AbstractCervical cancer morbidity and mortality in Lithuania is one of the biggest in the European Union. The main risk factor of cervical cancer is human papillomavirus (HPV). The deletion of the HPV E2 gene influences HPV DNA integration into the cell genome, as well as a rapid progression of cervical lesions. The purpose of this study is to determine HPV, its types, and HPV 16 integration in different grades of cervical intraepithelial neoplasias (CIN). 253 women with cytological lesions were involved in the study. After a histology, 31 women were diagnosed with CIN I, 35 with CIN II, and 51 with CIN III. The biggest prevalence of HPV infection was detected in women younger than 25 years old (69.7%) and in women with CIN II (90.9%). HPV 16 was detected in 67.8% of all cases, with the highest prevalence in CIN III (84.4%). A partial integration form was detected in 65.0% of HPV 16 infected women, a complete virus integration in 26.5%, and an episomal form in 8.4% of cases. Our study concludes that in all the cases confirmed using a histology, the partial virus integration form of CIN was identified the most. It was less frequently detected in CIN I cases (60.0%), but more frequently in CIN II and CIN III cases (72.8 and 69.3%, respectively).

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Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5530 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5530-5530

Author(s):

Jianjun Zhiang ◽

Elkanah Omenge ◽

Titus Maina ◽

Kapten Muthoka ◽

Stephen Kiptoo ◽

...

Keyword(s):

Cervical Cancer ◽

Cervical Dysplasia ◽

Hpv Infection ◽

Immunosuppressive Agent ◽

Sub Saharan Africa ◽

Hpv Testing ◽

Hpv 16 ◽

Kenyan Women ◽

Hpv Types ◽

Oncogenic Hpv

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.

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INHIBITORY ACTIVITY OF NATURAL ACTIVE COMPOUNDS AGAINST HUMAN PAPILLOMA VIRUS PSEUDOVIRUS AND NOVEL DOSAGE FORM FOR USE THEREWITH

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237213500361 ◽

2013 ◽

Vol 25 (03) ◽

pp. 1350036

Author(s):

Ming-Kuang Shih ◽

Yu-Chou Chao ◽

Ying-Chu Shih ◽

Kuo-Kuei Huang

Keyword(s):

Cervical Cancer ◽

Hela Cell ◽

Inhibitory Activity ◽

Dosage Form ◽

Hpv Infection ◽

Hela Cell Line ◽

Active Compounds ◽

Hpv 16 ◽

Papilloma Virus ◽

Screening Platform

Cervical cancer is a common cancer amongst women, accounting for 9% of female cancer death. There are certain risk factors for the development of cervical cancer, in which human papilloma virus (HPV) infection is believed to be a significant cause. This study aimed at evaluating the inhibitory activity of active compounds derived from Chinese herbs against HPV and the underlying mechanism. First, conventional screening platform which uses HeLa cell line in conjunction with MTT assay was used to evaluate the cytotoxicity of these natural compounds. Then, a novel screening platform, in which the HeLa cells were infected by HPV 16 pseudoviruses expressing green fluorescent protein, was employed to screen for active compounds capable of inhibiting the HPV 16 pseudovirus infection. Two compounds, baicalein and gallic acid, was found to exhibit significant inhibitory activity against HPV 16 pseudovirus with IC50 values of 8.2 and 8.9 μg/ml, respectively. In addition, these two compounds showed insignificant cytotoxicity on HeLa cell line. Screening experiments using a novel dosage form consisting of a hydrophilic PU foam and aquagel indicated that the aquagel also inhibited the HPV 16 pseudovirus infection. In sum, the natural active compounds and novel dosage form proposed by the present study imply a potential treatment for vaginal administration to prevent HPV infection and the diseases it caused.

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