Presence and persistence of HPV infection and <i>p53</i> mutation in cancer of the cervix uteri and the vulva

Milde‐Langosch, Karin; Albrecht, Kathrin; Joram, Simone; Schlechte, Horst; Giessing, Markus; Löning, Thomas

doi:10.1002/ijc.2910630507

Cited by 92 publications

(60 citation statements)

References 19 publications

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“…This has suggested the possibility that a viral agent such as BK virus (BKV), which infects the urinary tract and encodes tumor antigens that inactivate these tumor suppressors, may play a role in the etiology of prostate cancer. This would be very similar to the way in which the E6 and E7 oncogene products of human papillomavirus (HPV) inactivate p53 and pRB, respectively, in cervical carcinomas (13,22,27,37,49,72,73). It has been suggested that exposure to infectious agents can cause injury to the normal prostate epithelium, leading to the development of PIA (reviewed in reference 20).…”

mentioning

confidence: 81%

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

Das

Wojno²,

Imperiale

2008

J Virol

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Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes Rb1 and p53, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved. Previously, we detected BKV DNA in the epithelial cells of benign and proliferative inflammatory atrophy ducts of cancerous prostate specimens. In the present report, we demonstrate that BKV is present at a much lower frequency in noncancerous prostates. Additionally, in normal prostates, T-antigen (TAg) expression is observed only in specimens harboring proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. We further demonstrate that the p53 gene from atrophic cells expressing TAg is wild type, whereas tumor cells expressing detectable nuclear p53 contain a mix of wild-type and mutant p53 genes, suggesting that TAg may inactivate p53 in the atrophic cells. Our results point toward a role for BKV in early prostate cancer progression.

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confidence: 81%

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

Das

Wojno²,

Imperiale

2008

J Virol

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“…Recently, p53 mutation frequency in vulvar carcinomas is reported to be much higher compared with cervical carcinoma by 24%, (Lee et al, 1994), 53% (Milde-Langosch et al, 1995) and Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations 53% (Kagie et al, 1997). Vulvar cancer generally occurs in women over ten years older than women with cervical cancer, with a peak incidence between 65 and 75 years old (Langosch et al, 1995).…”

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confidence: 99%

“…Vulvar cancer generally occurs in women over ten years older than women with cervical cancer, with a peak incidence between 65 and 75 years old (Langosch et al, 1995). The incidence of high-risk HPVs, such as types 16 and 18, is lower in vulvar cancers than in cervical cancers (Nagano et al, 1996), the finding suggesting that mutation of p53 together with HPV may be involved in the carcinogenesis of the vulva.…”

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confidence: 99%

Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations

et al. 1999

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SummaryThe p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstrating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elderly women and a known human papillomavirus (HPV)-related malignancy, we analysed mutation of the p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean; 71 years, range; 60-96 years). The presence of HPV and its type were analysed by polymerase chain reaction (PCR)-based assay using the consensus primers for L1 region. Mutation of the p53 gene was analysed by PCR-based single-strand conformation polymorphism and DNA sequencing technique. Point mutation of the p53 gene was detected in 5 out of 46 (11%) cervical carcinomas: 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs (P = 0.36) whereas no mutation was found in 2 HPV negative cases. The mutated residues resided in the selective sequence known as a DNA-binding domain. The immunohistochemistry revealed the overexpression in cancer tissues positive for p53 mutation. All of the observed mutations of the p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. Although falling short of statistical significance reduces the strength of the conclusion, data presented here imply that p53 gene mutation, particularly along with intermediaterisk HPV types, may constitute one pathogenetic factor in cervical carcinoma affecting elderly women.

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“…2,9,10 Inconsistencies in p53 positivity rates in cervical as opposed to head and neck cancers can be explained by differences in the rates of p53 mutation. p53 mutations have rarely been detected in HPV-positive cervical cancers 11 but appear to coexist with HPV in some head and neck cancers. 12 The detection of p53 protein in cervical cancers by immunohistochemistry has mainly been attributed to the use of antibodies which detect stabilization of wild-type protein resulting from ongoing stress or disruption to proteins involved in p53 degradation, such as MDM2 11 in addition to mutations.…”

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confidence: 99%

The site of infection and ethnicity of the patient influence the biological pathways to HPV-induced mucosal cancer

Thompson

Cossart

et al. 2004

Modern Pathology

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High-risk human papillomaviruses are the causative agents of cervical cancer and are also believed to be aetiologically involved in a subset of squamous cell carcinomas of the head and neck region, especially the tonsil. Cervical cancers arise through disruption of the pathways of p53 and the product of the retinoblastoma gene by the human papillomavirus oncoproteins E6 and E7. It is generally assumed that the same pathways are involved in human papillomavirus-induced carcinogenesis at other mucosal surfaces. However, the patterns of expression of cell cycle proteins targeted by human papillomavirus E6 and E7 in cancers from different anatomic sites have been inconsistent, due to either biologic or technological factors. In this study, 73 human papillomavirus, 16-positive cervical squamous cell carcinomas (35 from Australian and 38 from Chinese women) were analysed for the expression of p53, pRb, p16 INK4A , p21 CIP1/WAF1 , p27 KIP1 and cyclin D1 by semiquantitative immunohistochemistry. Cervical cancers from Chinese women were found to be significantly more likely to overexpress p53, pRb, p21 and p27 than their Australian counterparts. These findings were compared with those from 31 human papillomavirus 16-positive tonsillar squamous cell carcinomas, all of Australian origin, tested using the same methodology. Comparisons of the tonsillar and combined cervical data showed that tonsillar cancers were significantly more likely to be p53-positive, whereas cervical cancers were significantly more likely to overexpress pRb, p16 and p27. When the tonsillar data were compared with cervical data from Australian women, the associations for p53 and pRb remained. These findings represent new evidence that the molecular pathways to human papillomavirus-induced mucosal cancer may be influenced by anatomic location and ethnicity.

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Presence and persistence of HPV infection and p53 mutation in cancer of the cervix uteri and the vulva

Cited by 92 publications

References 19 publications

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations

The site of infection and ethnicity of the patient influence the biological pathways to HPV-induced mucosal cancer

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