scholarly journals Human Papillomavirus 16 lineage D is associated with high risk of cervical cancer in the Brazilian Northeast region

Author(s):  
Luís Felipe Leite Martins ◽  
Miguel Ângelo Martins Moreira ◽  
Rodrigo Alves Pinho ◽  
Neilane Bertoni ◽  
Shayany Pinto Felix ◽  
...  

Abstract BackgroundLike HPV types, different lineages also appear to have different carcinogenic capabilities. Studies have shown that oncogenic HPV specific to the genotype lineage is associated with different risks for the development of cervical intraepithelial neoplasia (CIN2 / CIN3) and cervical cancer. This study aims to analyze the genetic diversity of HPV 16 genotype in cases of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer in women from the Northeast region of Brazil.Methods and ResultsA cross-sectional hospital-based study conducted in the Northeast region of Brazil from 2014 through 2016. In the sample, there were 196 cases of HPV-16 variant (59 cervical intraepithelial neoplasia - CIN2/CIN3 and 137 cases of cervical cancer). Difference of proportion test was used to compare groups of CIN2/CIN3 and cervical cancer by viral lineage (p-value <0.05) in respect to HPV-16 lineage prevalence.The percentage of lineage frequencies by histopathological diagnosis showed a borderline difference of lineage A in the CIN2/CIN3 group compared to the cervical cancer group (p = 0.053). In relation to lineage D, the proportion was higher in cancer cases (32.8%) compared to the CIN2/CIN3 group (16.9%), p-value of 0.023.ConclusionsHPV16 lineage A was the most frequent in both CIN2/CIN3 and cervical cancer samples, while lineage D predominated in cervical cancer, suggesting a possible association of HPV-16 lineage D with cervical cancer.

2009 ◽  
Vol 19 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Pavla Hublarova ◽  
Roman Hrstka ◽  
Pavla Rotterova ◽  
Leopold Rotter ◽  
Marie Coupkova ◽  
...  

Introduction:Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. We aimed to analyze the consequences of methylation of the E6 gene promoter in distinct stages of HPV-16-induced cellular transformation to assess its importance for disease progression.Methods:Human papillomavirus 16 was detected by sensitive polymerase chain reaction (PCR). Determination of E6 gene promoter methylation was analyzed by digestion with specific restriction endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was determined by quantitative real-time PCR.Results:Of 103 cervical smears from asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix carcinoma specimens. The incidence of HPV-16 in all lesions compared with asymptomatic women was statistically significant (P< 0.001, Pearsonχ2test). Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n = 23) in carcinomas; a statistical significance between lesions and healthy women was found (P< 0.001, Pearsonχ2test). Expression of E6 mRNA correlated with methylation status (P= 0.010, Mann-WhitneyUtest).Conclusions:We conclude that methylation of the E6 gene promoter in HPV-16 genome is a predictive biomarker for cervical cancer progression by regulating the expression of the E6 oncogene.


2018 ◽  
Vol 36 (3) ◽  
pp. 112-117
Author(s):  
SM Shahida ◽  
Nazma Parvin Ansary ◽  
Afrina Begum ◽  
Md Anisul Islam ◽  
Zannat Ara Rifat

Background: Persistent infection with high-risk Human Papilloma Virus (HPV) causes development of cervical cancer. Among the high risk group, HPV-16 accounts for 50% & HPV-18 accounts for 12% of cervical cancer.Objective: The current sudy aimed to evaluate the prevalence of HPV genotype 16 and 18 in high grade cervical intraepithelial neoplasia (CINII&III) and cervical cancer.Methods: This descriptive type of cross-sectional observational study was carried out in colposcopy clinic of Mymensingh Medical College Hospital (MMCH), Bangladesh, from July 2012 to June 2013. Women with colposcopically diagnosed high-grade CIN and clinically diagnosed cervical carcinoma were enrolled. Pregnant & menstruating women were excluded from this study. Colposcopy guided cervical biopsy were taken from high grade CIN with loop electrosugical excision procedure (LEEP) and wedge biopsy were taken from cervical cancer. All the specimen were reviewed by histopathologist to confirm the diagnosis. Extra sample of specimen were sent to the Department of Microbiology and Hygiene of Bangladesh Agriculture University, Mymensingh for the detection of HPV-16 & 18 DNA by Polymerase Chain Reaction (PCR).Result: Out of 71 samples, histopathologically 4.2% was diagnosed as chronic cervicitis, 8.5% CIN I, 26.8% CIN II, 16.9% CIN III, 40.8% squamous cell carcinoma and 2.8% adenocarcinoma of cervix. The results revealed that 30 cases were positive for HPV-16, 06 cases for HPV-18 and 04 cases for both. In this study, the prevalence of HPV- 16 & 18 infection was 56.3%. Infection found to be higher in women aged between 45 and 54 (P<0.01). Most of them were from low socioeconomic status (P<0.01) and married at an early age ranging from 11 to 15 (P<0.01). It was found that multiparity correlated higher rate of HPV positivity than only one or two pregnancy, but statistically it was not significant (P>0.05).Conclusion: The high prevalence of HPV-16 and 18 in high grade CIN and cervical cancer samples suggests that vaccination against HPV-16 and 18 may be effective in bringing down the cervical cancer incidence in Bangladesh.J Bangladesh Coll Phys Surg 2018; 36(3): 112-117


Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.


2009 ◽  
Vol 127 (5) ◽  
pp. 283-287 ◽  
Author(s):  
Andréa Cytryn ◽  
Fábio Bastos Russomano ◽  
Maria José de Camargo ◽  
Lucília Maria Gama Zardo ◽  
Nilza Maria Sobral Rebelo Horta ◽  
...  

CONTEXT AND OBJECTIVE: The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. DESIGN AND SETTING: Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. METHODS: ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. RESULTS: The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. CONCLUSION: The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.


2017 ◽  
Vol 9 (02) ◽  
pp. 104-110 ◽  
Author(s):  
Ankitha Hebbar ◽  
Venkataramappa Srinivasa Murthy

Abstract BACKGROUND: P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology. MATERIALS AND METHODS: Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated. RESULTS: The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction. CONCLUSION: Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.


2020 ◽  
Vol 30 (10) ◽  
pp. 1488-1492
Author(s):  
Haifeng Liu ◽  
Xia Meng ◽  
Jingyi Wang

IntroductionDNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the role of real time quantitative methylation detection of the PAX1 gene in cervical cancer screening.MethodsAll eligible patients who underwent multiple detections for cervical cancer were assigned to the normal cervical group (n=21), cervical intraepithelial neoplasia I group (n=7), cervical intraepithelial neoplasia II+III group (n=12), or invasive cervical cancer group (n=14) based on pathological gradings. The methylation level of the PAX1 gene was detected using the real time quantitative methylation specific polymerase chain reaction assay and assessed by △Cp value. The diagnostic performance of PAX1 methylation detection was compared with folic acid receptor mediated diagnosis, the Thinprep cytology test, and human papilloma virus (HPV) testing.ResultsThe △Cp value in the invasive cervical cancer group was (6.15±4.07), significantly lower than that in the other groups (F=26.45, p<0.001). The area under the curve (AUC) of PAX1 methylation detection was 0.902 (95% confidence interval (CI) 0.817–0.986; p<0.001), and sensitivity and specificity were 92.30% and 78.60% when the cut-off value of △Cp was 13.28. The AUC of PAX1 methylation detection was notably larger compared with 0.709 for folic acid receptor mediated diagnosis (95% CI 0.568–0.849, p=0.009), 0.702 for the Thinprep cytology test (95% CI 0.559–0.844, p=0.015), and 0.655 for HPV testing (95% CI 0.508–0.802, p=0.014).ConclusionThrough quantitative methylation specific polymerase chain reaction assay characterized by rapid screening and simple operation, the methylation detection of the PAX1 gene exhibited a higher diagnostic performance and may be a promising method for cervical cancer screening.


2006 ◽  
Vol 16 (3) ◽  
pp. 1032-1035
Author(s):  
S. N. Tabrizi ◽  
I. H. Frazer ◽  
S. M. Garland

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16–associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus–like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA–positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16–associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16–associated CIN 3 in patient population studied.


2015 ◽  
Vol 47 (1-2) ◽  
pp. 16-20
Author(s):  
Zannatul Ferdous Jesmin ◽  
Afroza Khanam ◽  
Eti Saha ◽  
Md Mokter Hossain

Cervical cancer develops from early precancerous lesion known as cervical intraepithelial neoplasia (CIN). Khulna Medical college Hospital provides primary screening for preventing cervical cancer and a secondary referral centre for management of CIN by colposcopy. Primary objective of this study was to do an audit between January 2012 to February 2014 to update clinical efficacy of colposcopy based diagnosis, treatment and follow up of 510 CIN cases and also to document any shortcomings in existing services and suggestion for early rectification. Colposcopic findings in our study group were: 309(60.6%) cases were CIN-1, 124 (24.3%) cases was CIN II, and 49 (9.6%) cases were CIN III. Suspicious of invasive lesion was in 7 (1.4%) abnormal looking cervix and biopsy was done in 21(4.1%). Treatment procedure was done with individualization of cases and options were cold coagulation, Loop electrosurgical excision procedure (LEEP), hysterectomy, biopsy and post treatment follow up. Histopathological diagnosis was documented in 387 cases, where CINI was found in 161 (31.6%), CIN II in 92 (18%), CIN III in 26 (5.1%), non specific Inflammatory cervicitis in 87(17.1%), Squamous cell carcinoma in 15(2.9%), abnormalities consistent with koilocytic atypia in 6 (12%) and reports missed in 123 (24.1%). Cases results showed Positive predictive value (PPV) of 53% and 68% respectively for low grade (CIN I) and high grade lesion (CIN II, III). 481 patient were eligible for post treatment follow up but only 99 (20.5%) patient came and among them 74 (74.7%) were colposcopically negative, 25 (25.2%) had residual CIN and Risk Ratio (RR) was 0.25. Colposcopy is gold standard for diagnosis of CIN but our screening program is opportunistic and far way from population based. Histopathological correlation were often inaccurate with colposcopic diagnosis in practice and about one third case reports were missed. Majority of women did not complete follow up protocol. Residual or recurrent CIN lesion in dropped out cases would be a concern in near future. DOI: http://dx.doi.org/10.3329/bmjk.v47i1-2.22557 Bang Med J (Khulna) 2014; 47 : 16-20


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