Human Papillomavirus Typing and Viral Gene Expression Analysis for the Triage of Women With Abnormal Results From Papanicolaou Test Smears to Colposcopy

2009 ◽  
Vol 133 (10) ◽  
pp. 1577-1586 ◽  
Author(s):  
Nick A. Antonishyn ◽  
Greg B. Horsman ◽  
Rod A. Kelln ◽  
Alberto Severini
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Diagnostic Methods ◽  
Screening Tools ◽  
Papanicolaou Test ◽  
Hpv 16 ◽  
Hpv E6 ◽  
Abnormal Results

Abstract Context.—A cascade of molecular tests for human papillomavirus (HPV), as a follow-up to Papanicolaou test screening, could eliminate unnecessary colposcopy. Tests based on detection of HPV E6 messenger RNA (mRNA) are already being used as screening tools, but there is a good biological rationale for expecting that an increase in the relative amounts of HPV E6 mRNA in cervical samples may better predict cancerous transformation. Objective.—To compare some of the available diagnostic methods and our novel method of relative quantification (RQ) of HPV gene expression for the effective triage of women with abnormal results from Papanicolaou tests to colposcopy. Design.—Sensitivities, specificities, and likelihood ratios were calculated for repeat Papanicolaou test smears, HPV DNA polymerase chain reactions, HPV genotyping, HPV-16 E6 mRNA detection, and the RQ of HPV-16 E6 mRNA calibrated to cellular RNA and DNA levels and standardized to viral load. Results.—Human papillomavirus genotype in combination with a repeat Papanicolaou test can be used to categorize most women (96%) with cervical intraepithelial neoplasia of grade 2 or higher for colposcopy while eliminating 44% of women with cervical intraepithelial neoplasia 1 or less. The presence of HPV-16 E6 mRNA (P < .001) and RQ of HPV-16 E6 mRNA (P < .001) displayed significant median differences among the various grades of cervical intraepithelial neoplasia. Further testing of women who are positive for HPV-16 demonstrated that the RQ of E6 mRNA has diagnostic potential when combined with Papanicolaou testing in populations with higher disease prevalence. Conclusions.—The RQ of HPV E6 mRNA and HPV genotype could be useful in a cascade of diagnostic testing designed to refer women with findings of cervical abnormalities for colposcopy or treatment while reducing triage numbers.

scholarly journals Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

2020 ◽  
Author(s):  
Satoshi Baba ◽  
Ayumi Taguchi ◽  
Akira Kawata ◽  
Konan Hara ◽  
Satoko Eguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Detection Rate ◽  
Expression Patterns ◽  
Epidemiologic Study ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Hpv 16 ◽  
Hpv Genotypes

Abstract Background Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. Methods In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6* , E1^E4 , and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated. Results The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1 . Conclusions We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

scholarly journals Prognostic Value of DNA and mRNA E6/E7 of Human Papillomavirus in the Evolution of Cervical Intraepithelial Neoplasia Grade 2

2014 ◽  
Vol 9 ◽  
pp. BMI.S14296 ◽  
Author(s):  
Michelle G. Discacciati ◽  
Ismael DCG. da Silva ◽  
Luisa L. Villa ◽  
Leandro Reis ◽  
Priscila Hayashi ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Small Sample ◽  
Low Grade ◽  
Cervical Smear ◽  
Hpv 16 ◽  
Regression Rate ◽  
Hpv E6

Objective This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). Methods This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Results Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status ( P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status ( P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. Conclusions The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

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.

Monitoring of patients with cervical intraepithelial neoplasia after excisional treatment

2021 ◽  
Vol 20 (1) ◽  
pp. 113-120
Author(s):  
N.V. Zarochentseva ◽  
◽  
L.K. Dzhidzhikhiya ◽  
V.N. Nabieva ◽  
◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
World Literature ◽  
Intraepithelial Neoplasia ◽  
Routine Screening ◽  
Diagnostic Methods ◽  
Almost Everywhere ◽  
Combined Test ◽  
Operative Monitoring

Cervical intraepithelial neoplasia (CIN) refers to precancerous changes in the cervix. After surgical treatment, a certain proportion of patients remain at risk of disease reccurence. Therefore, monitoring of patients after CIN surgery is an important and necessary part of their management tactics. Objective. Review of world literature on modern approaches to patients monitoring after using excisional methods of CIN treatment. Materials and methods. The information material includes data from scientific articles on the subject available in Pubmed and published over the past 20 years. Results. The analysis of data contained in modern literature on the frequency and risk factors for the development of reccurent CIN after excisional methods of treatment, diagnostic methods, the timing of follow-up examinations during post-operative monitoring, the main approaches to monitoring in different countries and the effectiveness of the proposed strategies for postoperative follow-up of patients after treatment was conducted. It was established that the approaches to the observation of this category of patients differ in various countries. Almost everywhere, the priority tool for monitoring of patients with CIN after treatment is a combined test, which involves a joint use of cytology and human papillomavirus tests. The main difference between countries is the timing of the first post-treatment follow-up visit. In some countries a follow-up visit is recommended within 24 months, while in others it is suggested to return to routine screening if the primary combined test is negative. Conclusion. Despite existing disagreements, the proposed post-operative monitoring strategies for CIN patients provide a fairly high percentage of “healing” and return to routine screening. Key words: human papillomavirus, monitoring, cervical cancer, cervical intraepithelial neoplasia, excisional treatment

scholarly journals Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e015867 ◽  
Author(s):  
Matti Lehtinen ◽  
Camilla Lagheden ◽  
Tapio Luostarinen ◽  
Tiina Eriksson ◽  
Dan Apter ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Registry ◽  
Vaccine Efficacy ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Hpv 16 ◽  
Link Type

ObjectiveDue to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.

scholarly journals Differential expression of human papilloma virus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

2020 ◽  
Author(s):  
Satoshi Baba ◽  
Ayumi Taguchi ◽  
Akira Kawata ◽  
Konan Hara ◽  
Satoko Eguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Detection Rate ◽  
Expression Patterns ◽  
Epidemiologic Study ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Carcinogenic Risk ◽  
Hpv 16 ◽  
Hpv Genotypes

Abstract Background: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.Methods: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.Results: The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.Conclusions: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

2006 ◽  
Vol 16 (3) ◽  
pp. 1032-1035
Author(s):  
S. N. Tabrizi ◽  
I. H. Frazer ◽  
S. M. Garland
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
High Grade ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Human Papillomavirus 16 ◽  
Serologic Response ◽  
Poor Predictor ◽  
Hpv Types

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.

Inverse relationship between the expression of the human papillomavirus type 16 transcription factor E2 and virus DNA copy number during the progression of cervical intraepithelial neoplasia

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1825-1832 ◽  
Author(s):  
Mark Stevenson ◽  
Lucy C. Hudson ◽  
Julie E. Burns ◽  
Roy L. Stewart ◽  
Michael Wells ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Lower Grade ◽  
Invasive Squamous Cell Carcinoma ◽  
Hpv 16 ◽  
E2 Protein ◽  
Hpv Dna ◽  
Human Papillomavirus Type 16 ◽  
Invasive Carcinomas

The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, which had been characterized histologically as normal, various grades of cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma, was examined by using (i) a novel antibody against the HPV-16 E2 protein, (ii) sensitive HPV-16 DNA in situ hybridization and (iii) microdissection/PCR for the E2 ORF. The data indicate that E2 protein expression is highest in koilocytes in lower-grade CIN (I), but decreases with increasing grade, whereas the detection of HPV DNA is delayed until CIN I/II, rising to the highest levels in carcinoma cells. Co-localization of E2 with HPV-16 DNA-positive cells was most commonly observed in koilocytes in CIN II lesions. PCR analyses of microdissected epithelium from the same or serial sections indicated that E2 ORFs were retained in an intact form in a number of higher-grade CIN lesions and invasive carcinomas.

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