Possible prognostic significance of human papillomavirus type in cervical cancer

Barnes, Willard A.; Delgado, Gregorio; Kurman, Robert J.; Petrilli, Edmund S.; Smith, Donna M.; Ahmed, Susan W.; Lörincz, Attila T.; Temple, Gary F.; Jenson, A. Bennett; Lancaster, Wayne D.

doi:10.1016/0090-8258(88)90225-9

Cited by 130 publications

(48 citation statements)

References 14 publications

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“…Firstly, the lesions in patients with ACIS and coexisting CIN may show a faster progression, leading to detection at a younger age. This has been described previously for HPV 18-related lesions (Barnes et al, 1988), but we did not find a difference in HPV 18 prevalence between patients with ACIS alone or ACIS and coexisting CIN. Secondly, the involvement of the squamous epithelium may be the reason for the detection of ACIS with coexisting CIN at a younger age, since ecto-cervical lesions are more easily detected.…”

Section: Discussionmentioning

confidence: 36%

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

Bekkers¹,

Bulten²,

Tilburg

et al. 2003

Br J Cancer

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The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF 10 LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with highgrade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions. . Numerous studies have suggested that the development of squamous cervical carcinoma is preceded by cervical intraepithelial neoplasia (CIN) (Wright et al, 2002;Bosch et al, 2002).The frequency of hr-HPV genotypes in CIN lesions has been studied previously and its detection rate rises with increasing severity of the CIN lesion (Bekkers et al, 2002a;Bosch et al, 2002;Wright et al, 2002). Only limited studies are available on the frequency of hr-HPV genotypes in premalignant glandular lesions and the number of patients in most studies is rather low (see Table 1) (Colgan and Lickrish, 1990;Leary et al, 1991;Higgins et al, 1992;Duggan et al, 1995;Anciaux et al, 1997;McLachlin et al, 1997;Pirog et al, 2000;Riethdorf et al, 2000Riethdorf et al, , 2002Madeleine et al, 2001). High-risk human papillomavirus was detected in 66 -100% of patients with ACIS (Anciaux et al, 1997;Riethdorf et al, 2000). Approximately 48% of all women diagnosed with ACIS have coexisting squamous lesions (Colgan and Lickrish, 1990;Leary et al, 1991;Higgins et al, 1992;Duggan et al, 1995;Anciaux et al, 1997;McLachlin et al, 1997;Pirog et al, 2000;Riethdorf et al, 2000Riethdorf et al, , 2002Madeleine et al, 2001), but the frequency of specific hr-HPV genotypes in patients with ACIS has not been studied in relation with the presence or absence of coexisting CIN lesions. In this stu...

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Section: Discussionmentioning

confidence: 36%

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

Bekkers¹,

Bulten²,

Tilburg

et al. 2003

Br J Cancer

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“…Initial studies showed that the efficiency of degradation mediated by oncogenic E6 proteins was related, in part, to the strength of interaction between their C-terminal residues and the PDZ domains of their targets; thus HPV-18 E6, which has a perfect consensus PDZ-binding domain, binds and induces degradation of Dlg more efficiently than does HPV-16 E6, which has a degenerate PDZ-binding domain (Gardiol et al, 1999;Pim et al, 2000;Thomas et al, 2001). This was an important finding since there is evidence to suggest that HPV-18 produces more aggressive tumours than does HPV-16 (Barnes et al, 1988;Kurman et al, 1988;Burnett et al, 1992;Zhang et al, 1995) even though HPV-16 E6 induces the degradation of the p53 tumour suppressor more efficiently than does HPV-18 E6 (Scheffner et al, 1990). Several recent studies have also shown that the high-risk E6 proteins can target several other PDZ domain-containing proteins for proteasome-mediated degradation.…”

Section: Introductionmentioning

confidence: 65%

Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating different E6 cellular target proteins

2002

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The ability of HPV E6 oncoproteins to induce the degradation of PDZ domain-containing MAGUK proteins correlates with their malignant potential. We previously showed that the HPV-6 E6 protein, when provided with the PDZ-binding domain from HPV-18 E6, acquires the ability to bind the Discs Large (Dlg) tumour suppressor and target it for degradation. Based on this finding we have extended this analysis to E6 proteins from a variety of different papillomavirus types. Cloning a PDZ-binding sequence onto the C-terminus of E6 proteins derived from low-risk mucosal, and low and high-risk cutaneous papillomavirus types, enables them to bind Dlg and a second MAGUK family member, MAGI-1. This renders the mucosally-derived low-risk chimaeric HPV E6 proteins capable of targeting Dlg for degradation, but they are unable to induce significant levels of degradation of MAGI-1. In contrast, none of the E6 proteins derived from cutaneous papillomavirus types induce significant degradation of either MAGI-1 or Dlg when provided with a PDZ-binding domain. These results demonstrate significant differences, both between mucosal and cutaneous HPV E6 proteins and in the pathways required for Dlg and MAGI-1 degradation.

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“…Certainly, there is an extensive literature which indicates that HPV-18 is generally more active than HPV-16 in a variety of transformation assays (Barbosa and Schlegel, 1989;Villa and Schlegel, 1991). In addition, there are also several reports which indicate that HPV-18-containing cervical tumours have a more aggressive phenotype and are also more prone to recurrence than HPV-16-containing tumours (Barnes et al, 1988;Kurman et al, 1988;Burnett et al, 1992;Zhang et al, 1995). Since the only biochemical activity of HPV-18 which correlates with this trend, so far, is the increased activity of E6 with respect to DLG, it is tempting to speculate that it is this association which is critical for the malignant progression of HPV induced tumours.…”

Section: Discussionmentioning

confidence: 99%

HPV E6 targeted degradation of the discs large protein: evidence for the involvement of a novel ubiquitin ligase

et al. 2000

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The Discs Large (DLG) tumour suppressor protein is targeted for ubiquitin mediated degradation by the high risk human papillomavirus (HPV) E6 proteins. In this study we have used a mutational analysis of E6 in order to investigate the mechanism by which this occurs. We ®rst show that the dierences in the anities of HPV-16 and of HPV-18 E6 proteins for binding DLG is re¯ected in their respective abilities to target DLG for degradation. A mutational analysis of HPV-18 E6 has enabled us to de®ne regions within the carboxy terminal half of the protein which are essential for the ability of E6 to direct the degradation of DLG. Mutants within the amino terminal portion of E6 which have lost the ability to bind the E6-AP ubiquitin ligase, as measured by their ability to degrade p53, nonetheless retain the ability to degrade DLG. Signi®cant levels of DLG degradation are also obtained using wheat germ extracts which lack E6-AP. Finally, we show that the transfer of the DLG binding domain onto the low risk HPV-6 E6 confers DLG binding activity to that protein and, most signi®cantly, allows HPV-6 E6 to target DLG for degradation. These results indicate that E6 mediated degradation of DLG does not involve the E6-AP ubiquitin ligase and, in addition, shows that the high and low risk HPV E6 proteins most likely share a common cellular intermediary in the ubiquitin pathway. Oncogene (2000) 19, 719 ± 725.

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Possible prognostic significance of human papillomavirus type in cervical cancer

Cited by 130 publications

References 14 publications

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating different E6 cellular target proteins

HPV E6 targeted degradation of the discs large protein: evidence for the involvement of a novel ubiquitin ligase

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