Papillomavirus infections — a major cause of human cancers

Hausen, Harald zur

doi:10.1016/0304-419x(96)00020-0

Cited by 1,083 publications

(1,181 citation statements)

References 285 publications

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“…Conversely, HPV is well known to be a cause of cervical carcinoma. 1 In particular, persistent detection of high-risk HPV types is a strong predictor of the development of high-grade cervical precancerous lesions and invasive cervical carcinoma. 9,10 Therefore, in primary cervical carcinoma screening, HPV-DNA testing has been used and the sensitivity and specificity are estimated to be higher and lower, respectively, than that of the conventional Pap smear test.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

Yoshida

Fukuda

Sano

et al. 2004

Cancer

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Section: Discussionmentioning

confidence: 99%

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

Yoshida

Fukuda

Sano

et al. 2004

Cancer

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“…Some of the HPV encoding proteins, i.e. E6, E7 and E5 from the`high risk' HPVs have been shown to exhibit transforming activities (for review see Howley, 1996;zur Hausen, 1996). It has been demonstrated that E6 protein from the`high risk' but not the`low risk' HPVs has the capacity to bind to the tumor suppressor p53 and promote its degradation through ubiquitinmediated proteolysis (Howley, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that E6 protein from the`high risk' but not the`low risk' HPVs has the capacity to bind to the tumor suppressor p53 and promote its degradation through ubiquitinmediated proteolysis (Howley, 1996). Expression of HPV-16 E6 alone is able to immortalize human mammary epithelial cells, or induce anchorageindependent growth of NIH3T3 cells (Howley, 1996;zur Hausen, 1996). It has also been shown that HPV-16 E6 inhibits the serum-and calcium-induced di erentiation of human keratinocytes (Sherman and Schlegel, 1996).…”

Section: Introductionmentioning

confidence: 99%

The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α

et al. 1999

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We have examined the e ects of human papilloma virus (HPV) E6 proteins on interferon (IFN) signaling. Here we show that expression of the`malignant' HPV-18 E6 in human HT1080 cells results in inhibition of Jak-STAT activation in response to IFN-a but not IFN-g. This inhibitory e ect is not shared by the`benign' HPV-11 E6. The DNA-binding and transactivation capacities of the transcription factor ISGF3 are diminished in cells expressing HPV-18 E6 after IFN-a treatment as a result of decreased tyrosine phosphorylation of Tyk2, STAT2 and STAT1. However, HPV-18 E6 does not a ect the induction of tyrosine phosphorylation and DNA-binding of STAT1 by IFN-g. In addition, HPV E6 proteins physically interact with Tyk2. This interaction takes place preferably with HPV-18 E6 and to a lesser extent with HPV-11 E6. The E6/Tyk2 interaction requires the JH 6 -JH 7 domains of Tyk2, which are important for Tyk2 binding to the cytoplasmic portion of IFN-a receptor 1 (IFNAR1). These ®ndings demonstrate an inhibitory role of HPV-18 E6 in the IFN-a-induced Jak-STAT pathway, which may be explained, at least in part, by the ability of E6 to interact with and impair Tyk2 activation.

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“…Upon sexual transmission, HPV-16 (and other oncogenic types of sexually transmitted HPVs) infects the basal and parabasal cells of the cervical mucosa where transcription and translation of the early antigens of HPV-16 leads to cellular atypia followed by preinvasive neoplasia. 2 Cellular transformation is initiated by the three viral oncoproteins, E5, E6 and E7, which cause dysregulation of cell cycle control. 2,3 The oncoproteins of HPV-16 being causative for transformation of HPV-16-infected cells are thereby natural targets for active immunotherapy of HPV-16-associated cervical cancer.…”

mentioning

confidence: 99%

“…2 Cellular transformation is initiated by the three viral oncoproteins, E5, E6 and E7, which cause dysregulation of cell cycle control. 2,3 The oncoproteins of HPV-16 being causative for transformation of HPV-16-infected cells are thereby natural targets for active immunotherapy of HPV-16-associated cervical cancer.…”

mentioning

confidence: 99%

DNA vaccines against the human papillomavirus type 16 E6 or E7 oncoproteins

et al. 2004

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DNA vaccines expressing the E6 or E7 oncoproteins of human papilloma virus type 16 (HPV-16) in either their wild-type form or fused to sequences that affect intracellular trafficking were tested for induction of protective immunity against tumor cell challenge in two models based on BALB/c and C57Bl/6 mice. The DNA vaccines to E7 gave uniformly disappointing results, while the DNA vaccine that expressed E6 linked to a viral leader sequence protected BALB/c mice against tumor cell challenge given before or after vaccination. The efficacy of this vaccine could be enhanced by a DNA vector prime/viral vector boost regimen. In contrast, priming of mice with the DNA vaccines to E7 reduced the efficacy of a viral vector expressing the same antigen. C ervical cancer is most commonly a consequence of sexually transmitted, persistent infections with oncogenic types of HPVs, most notably HPV-16. 1 Cervical cancer is the second most common cause of cancer death in women worldwide, claiming approximately 300,000-500,000 lives each year. Upon sexual transmission, HPV-16 (and other oncogenic types of sexually transmitted HPVs) infects the basal and parabasal cells of the cervical mucosa where transcription and translation of the early antigens of HPV-16 leads to cellular atypia followed by preinvasive neoplasia. 2 Cellular transformation is initiated by the three viral oncoproteins, E5, E6 and E7, which cause dysregulation of cell cycle control. 2,3 The oncoproteins of HPV-16 being causative for transformation of HPV-16-infected cells are thereby natural targets for active immunotherapy of HPV-16-associated cervical cancer.A number of vaccine modalities to HPV-16 oncoprotein-expressing tumor cell lines have been tested in preclinical animal models focusing mainly on vaccines to E7, 4-10 although studies with vaccines to E6 4,7,10 and E5 11 have also been reported. Our vaccine effort initially focused on viral recombinant vaccines expressing the E6 or E7 protein. They showed that E1-deleted adenoviral vectors to E7 induce potent and tumor-protective CD8 þ T-cell responses in C57Bl/6 mice. In contrast, BALB/c mice displayed partial CD4 þ T-cell-mediated protection induced by vaccinia or adenoviral recombinant vaccines expressing the E6 of HPV-16 but could not be protected by the vaccines to E7. 7 In this report, we extended our studies to DNA vaccines expressing the E7 or E6 proteins of HPV-16. In addition to those expressing wild-type versions of the oncoproteins, we also tested DNA constructs that express the oncoproteins linked to various polypeptides that affect intracellular trafficking. In one construct, the oncoproteins were fused to a viral leader sequence that prevents nuclear localization and instead affects secretion. A second modification involved addition of a leader sequence and the lysosome-associated membrane protein (LAMP)-1, which channels proteins upon secretion into lysosomes resulting in improved association with MHC class II determinants. This modification, used previously for HPV-16 E7 vaccines, was shown ...

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Papillomavirus infections — a major cause of human cancers

Cited by 1,083 publications

References 285 publications

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-α

DNA vaccines against the human papillomavirus type 16 E6 or E7 oncoproteins

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