T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Steele, Jane C.; Mann, Christopher H.; Rookes, Susan M.; Rollason, T. P.; Murphy, Denis J.; Freeth, MG; Gallimore, Phillip H.; Roberts, Sally

doi:10.1038/sj.bjc.6602679

Cited by 76 publications

(60 citation statements)

References 56 publications

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“…These findings are similar to data reported in previous studies (36,37,43,44) in which healthy women were more likely to show positive Tcell proliferative responses to HPV16 compared to women with abnormal cervical cytology. In addition, our findings are also consistent with prior studies that have reported lymphoproliferative responses to HPV16 peptides to be correlated with current status of HPV infection (14).…”

Section: Discussionsupporting

confidence: 91%

“…As illustrated in Table 2, 47% (28/60) of HPV16-negative patients were positive "responders" to E6 compared to only 14% (2/14) of HPV16-positive patients, χ 2 (1) = 4.94, p < .03. This association was also observed for E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57] and L1 382-396 peptides, both χ 2 (1)s > 5.40, ps < .03.…”

Section: T-cell Response To Hpv-16 Peptides In Relation To Participansupporting

confidence: 59%

“…HPV types targeted in the high risk probe cocktail included HPV 16,18,31,33,35,39,45,51,52,56,58,59, 68. HPV types targeted in the low risk probe cocktail included HPV 6,11,42,43,44. Among cases that were positive for high-risk subtypes, we tested for the presence of HPV16 with an HPV16-specific probe using the same methodology.…”

Section: Methodsmentioning

confidence: 99%

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Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Fang¹,

Miller²,

Bovbjerg³

et al. 2008

ann. behav. med.

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Background-Infection with high-risk subtypes of human papillomavirus (HPV) is a central factor in the development of cervical neoplasia. Cell-mediated immunity against HPV16 plays an important role in the resolution of HPV infection and in controlling cervical disease progression. Research suggests that stress is associated with cervical disease progression, but few studies have examined the biological mechanisms that may be driving this association.

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Section: Discussionsupporting

confidence: 91%

Section: T-cell Response To Hpv-16 Peptides In Relation To Participansupporting

confidence: 59%

See 1 more Smart Citation

Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Fang¹,

Miller²,

Bovbjerg³

et al. 2008

ann. behav. med.

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“…23 It has been suggested that the HPV 16 immune response is dependent on the dose of antigen, because the frequency of CD41 T-cell responses was higher in cervical cancer patients compared with high-grade CIN patients. 8,10 We previously found that high HPV mRNA expression is associated with worse survival. 23 Apparently, the stimulating effect of high levels of oncogene on tumor growth outweighs the possible effect on the immune system that could lead to reduced growth.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 In a minority of patients with high grade Cervical Intraepithelial Neoplasia (CIN) as well as in half of the cervical cancer patients a specific T-cell response to E6 and E7 can be detected. [8][9][10] Cell-surface expressed human histocompatibility leukocyte antigen (HLA) Class I and Class II molecules form the target molecules for CD81 cytotoxic T-cells and CD41 T-cells, respectively. HLA Class I molecules consist of a glycoprotein heavy chain and a b 2 -microglobulin (b 2 M) light chain.…”

mentioning

confidence: 99%

Circulating human papillomavirus type 16 specific T‐cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

Boer¹,

Jordanova²,

Poelgeest³

et al. 2007

Intl Journal of Cancer

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Human papillomavirus (HPV) is a necessary factor in the pathogenesis of cervical cancer. Circulating HPV-specific T-cells responding to the E6 and E7 HPV proteins can be detected only in half of cervical cancer patients. Potential explanations for the absence of this response are lack of sufficient amounts of antigen to activate the immune response or local immune escape mechanisms. We studied the relationship between HPV 16 E6/E7 oncogene mRNA expression, human leukocyte antigen (HLA) expression on tumor cells and the presence of circulating E6-and E7-specific T-cell responses in cervical cancer patients. The amount of antigen was assessed by HPV E6/E7 mRNA expression levels measured by quantitative polymerase chain reaction. HLA Class I and Class II expression on tumor cells was analyzed by immunohistochemistry. A proliferative HPV-specific T-cell response was detected in 15/29 patients. The amount of HPV E6/E7 mRNA was not related to the presence of immune response. HLA Class I expression was downregulated in 19 patients and completely lost in 7 patients. HLA Class II expression was upregulated in 18 patients. HLA Class I expression on tumor cells showed a strong correlation with immunity (p 5 0.001). Explicitly, all patients with complete HLA loss lacked HPV specific T-cell responses. The presence of circulating HPV-specific T-cells might reflect ongoing antitumor response that is sustained by CD81 T-cells killing HLA Class I positive cancer cells. We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; cervical cancer; HLA; T-cell response; mRNA expression Cervical cancer is the second most common cancer in women worldwide, with 400,000 new cases diagnosed each year. Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, as it is detected in 99.7% of cases. 1 HPV Type 16 is the most prevalent type, accounting for 50% of all cervical cancers. 2 The 2 viral oncoproteins, E6 and E7 are constitutively expressed and inactivate the tumor suppressor proteins p53 and pRb, respectively, causing deregulation of the cell cycle. 3 The E6 and E7 proteins are transcribed from 1 shared transcript. In addition to the full-length E6/E7 mRNA, HPV 16 generates 2 spliced transcripts, referred to as E6*I and E6*II. The function of the spliced transcripts is not well understood. 4,5 Therapeutic vaccinations aim at generating specific T-cell responses to these oncogenes. 6 The cellular immune response is likely to be an important mechanism for the clearance of established HPV infections. It has been shown that immunosuppressed individuals are more likely to have persistent HPV infections, whereas a T-cell response can usually be detected in healthy individuals. 6,7 In a minority of patients with high grade Cervical Intraepithelial Neoplasia (CIN) as well as in half of the cervical cancer patients a specific T-cell response to E6 and E7 can be detected. [8][9][10] Ce...

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The interplay between HPV and host immunity in head and neck squamous cell carcinoma

Andersen

Sølling

Ovesen

et al. 2013

Intl Journal of Cancer

104

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Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16-infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations. This review summarizes the literature concerning the adaptive immune response against HPV in the context of HNSCC, with a focus on the T-cell response. Recent studies have shown that a broad repertoire of tumorinfiltrating HPV-specific T-cells are found in nearly all patients with HPV-positive tumors. A systemic response is found in only a proportion of these. Furthermore, the local response is more frequent in OPSCC patients than in cervical cancer patients and HPV-negative OPSCC patients. Despite this, tumor persistence may be facilitated by abnormalities in antigen processing, a skewed T-helper cell response, and an increased local prevalence of T-regulatory cells. Nonetheless, the immunologic profile of HPV-positive vs. HPV-negative HNSCC is associated with a significantly better outcome, and the HPV-specific immune response is suggested to play a role in the significantly better response to therapy of HPV-positive patients. Immunoprofiling may prove a valuable prognostic tool, and immunotherapy trials targeting HPV are underway, providing hope for decreasing treatment-related toxicity.

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T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Cited by 76 publications

References 56 publications

Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Circulating human papillomavirus type 16 specific T‐cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

The interplay between HPV and host immunity in head and neck squamous cell carcinoma

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