Physical Status and Expression of HPV Genes in Cervical Cancers

Park, Jong Sup; Hwang, Eun Seong; Park, Sue Nie; Ahn, Hee Kyung; Um, Soo‐Jong; Kim, Chan Joo; Kim, Seung Jo; Namkoong, Sung Eun

doi:10.1006/gyno.1996.4596

Cited by 125 publications

(109 citation statements)

References 35 publications

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“…Besides, the use of these consensus primers may leave some important oncogenic HPV types undetected because of loss of the L1 sequence during viral integration. In clinical practice this can be critical, since integrated HPV 16/18 DNA has been revealed in various stages of dysplasia (Nagao et al, 2002;Gallo et al, 2003) and is shown to be common in patients with cervical carcinomas (Park et al, 1997;Kalantari et al, 1998;Walboomers et al, 1999). Therefore, the use of type-specific PCR, directed against one of the early-region genes (preferentially E6 and E7), is always recommended.…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from 190 cervical cones

et al. 2004

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In this study, we investigated the presence of E6/E7 transcripts of seven common high-risk human papillomavirus (HPV) types in 190 cervical biopsies. The RNA-based real-time nucleic acid sequence-based amplification assay (NASBA) and type-specific PCR, both detecting HPV 16, 18, 31, 33, 45, 52, and 58, as well as consensus PCR, were performed on all 190 biopsies. High accordance between type-specific and consensus PCR confirms that the HPV types included in this study are the most common types present in cervical dysplasia. Furthermore, we see a clear increase in the incidence of HPV, both DNA and RNA, along with the histological severity of dysplasia. HPV RNA was detected in all but two PCR-positive cases, confirming that the virus exerts E6/E7 mRNA expression in cases of high-grade dysplasia. Out of 19 women given a normal or borderline diagnosis at conisation, only four were found HPV positive, which may suggest that unnecessary conisations can possibly be reduced by introducing HPV testing into the preoperative routine assessment. Human papillomavirus (HPV) infections are associated with the development of cervical neoplasia and are a necessary factor in the aetiology of cervical carcinoma (Walboomers et al, 1999;Bosch et al, 2002;zur Hausen, 2002). The most frequent HPV types found in high-grade cervical intraepithelial dysplasia (CIN II/III) and in cervical carcinomas are HPV 16, 18, 31, 33, and 45, which are often referred to as high-risk HPV or cancer-associated HPV types. However, the association between a positive HPV DNA test and the risk of subsequent development of dysplasia is partly unknown; the presence of HPV DNA does not necessarily indicate a risk for developing a more severe lesion. In fact, HPV is a very common virus among sexually active women and most infections are transient and asymptomatic (zur Hausen, 1991;Ho et al, 1998;Moscicki et al, 1998). Only very few infections cause morphologic changes in the epithelium and only a small percent of these will eventually develop cervical cancer (Bosch et al, 1995). On the other hand, several studies have shown that in cervical carcinogenesis, the expression of HPV E6 and E7 ORF is required for cell transformation and immortalisation (zur Hausen, 1988;Munger et al, 1989;Stoler et al, 1992). Consequently, persistent expression of these oncogenes may serve as an indicator of progression to CIN and invasive cancer (Sotlar et al, 1998), and detection of E6 and E7 mRNA transcripts may therefore be of higher prognostic value than the detection of HPV DNA. Moreover, new methods for preservation of RNA in cells have made gene expression analysis more feasible.In this study, we investigated the presence of high-risk HPV E6/E7 transcripts in cervical biopsies from patients undergoing conisation. The analysis was performed on a biopsy taken from the ectocervix/transformation zone at the time of conisation, and the pathological diagnosis of this particular biopsy was not always representative for the existing lesion that was later revealed in the cone. This s...

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Section: Discussionmentioning

confidence: 99%

Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from 190 cervical cones

et al. 2004

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“…Inactivation of the p53 function is important in the pathogenesis of cervical carcinoma (35). HPVs are heavily implicated in the etiology of this tumour (35,36). Protein E2 of oncogenic HPV inhibits the expression of oncoprotein E6 and E7 genes and suppresses the proliferation of cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Intratumour Microvessel Density and Haemoglobin Level in Carcinoma of the Uterine Cervix

et al. 2002

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“…All ACIS were HPV 18 positive: HPV DNA (notably HPV 18) is usually present in the integrated form in endocervical neoplasia. 29 Ki-67 and p16 ink4a immunohistochemistry…”

Section: Tissue Materialsmentioning

confidence: 99%

HPV in situ hybridization: Impact of different protocols on the detection of integrated HPV

Hopman

Kamps

Smedts³

et al. 2005

Intl Journal of Cancer

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Although there is consensus that HPV integration is common in invasive cervical carcinomas and uncommon or absent in lowgrade uterine cervical intraepithelial neoplasia (CIN I), estimates for HPV integration in CIN II/III range from 5 to 100% using different PCR-based and in situ hybridization (ISH) approaches. It has been suggested that HPV integration can be identified using ISH by scoring of punctate signals. The increased sensitivity of fluorescence ISH (FISH) methods, allowing the detection of single copies of HPV, complicates the distinction between integrated and episomal HPV. Recently it has been suggested that, in such assays, the signals originating from integrated virus can be hidden in a background of episomal HPV. We therefore compared 2 different FISH protocols for the detection of integrated HPV in a series of CIN II/III lesions: 1) a mild protocol in which episomal HPV and RNA is retained and 2) a harsh protocol that extensively extracts proteins and RNA, and which promotes the partial loss of episomal HPV but not integrated HPV. A series of 28 HPV 16/18 positive CIN II/III lesions (17 solitary lesions and 11 lesions adjacent to microinvasive carcinoma) were studied. A punctate signal pattern was identified in 7 of these lesions with both protocols. Punctate signal was also present in control samples from lesions that are known to be associated with HPV integration (invasive squamous cell carcinoma (n ¼ 3), adenocarcinoma in situ (n ¼ 3), and invasive adenocarcinoma (n ¼ 1). HPV RNA contributed significantly to the intensity of punctate FISH signal, especially when applying the mild protocol, as shown by omitting DNA denaturation, including RNase pretreatment steps and measuring the fluorescence signal intensity. Also, HPV RNA was frequently detected in addition to episomal/integrated HPV DNA in the majority of the other 21 CIN II/III lesions; this resulted in intense granular/ diffuse FISH signals throughout the epithelium. However, in 7 of these lesions, the harsh protocol gave a more consistent punctate pattern in cells throughout the full thickness of the epithelium. This supports the hypothesis that the harsh protocol unmasks integrated HPV more efficiently by extracting RNA and episomal HPV. Overall, with this harsh protocol, a clonally expanded population of cells containing punctate HPV signals was found in 5 of 17 (29%) solitary CIN II/III lesions and in 9 of 11 (88%) CIN II/ III lesions associated with microinvasive carcinoma. Combining these data with the results from our previous study, with the harsh protocol in 7 of 40 (18%) Several premalignant stages can be distinguished in the development of carcinoma of the uterine cervix. These include cervical intraepithelial neoplasia grades I, II and III (CIN I-III), also designated low-grade squamous intraepithelial lesions (LSIL, comprising CIN I) and high grade SIL (HSIL, comprising CIN II-III). 1-4Nearly all invasive cervical carcinomas (ICCs) and CIN grade II/ III lesions contain human papillomavirus (HPV) DNA. Epidemiological studies ...

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Physical Status and Expression of HPV Genes in Cervical Cancers

Cited by 125 publications

References 35 publications

Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from 190 cervical cones

Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from 190 cervical cones

Prognostic Significance of Intratumour Microvessel Density and Haemoglobin Level in Carcinoma of the Uterine Cervix

HPV in situ hybridization: Impact of different protocols on the detection of integrated HPV

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