Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia

Zumbach, Klaus; Kisseljov, F. L.; Sacharova, O. V.; Shaichaev, G.; Semjonova, L. A.; Павлова, Л. С.; Pawlita, Michael

doi:10.1002/(sici)1097-0215(20000201)85:3<313::aid-ijc3>3.0.co;2-w

Cited by 60 publications

(61 citation statements)

References 24 publications

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“…20 This problem makes it also difficult to compare the strength of the association of CIN3/CIS and ICC with HPV versus the other STIs considered in the present paper and for which the presented ORs are less prone to be decreased by lack of antibody detection. Seropositivity to the E6 oncogene of HPV16 showed by far the strongest association with ICC risk, in agreement with previous findings on ICC 21,24,25 and partly with cancer of the oropharynx. 12,[26][27][28] However, although HPV16 is known to be involved in about 50% of ICC, HPV16 E6 antibodies were detected in only 11% of ICC pointing to the substantial lack of sensitivity not only of L1 serology, but also of E6 serology.…”

Section: Epidemiologysupporting

confidence: 92%

“…Other studies using other designs have also found associations between antibodies to HPV16/18 E6/E7 proteins and ICC showing however a range of generally low sensitivity values when compared with HPV DNA detection in the tumor. 21,24,25 Consistent with these results which concern cervical cancer, two recent studies, one using also the EPIC cohort 12 and the other one using a multicentric case-control design, 26 found strong associations between HPV16 E6 seropositivity and oropharyngeal cancer. In the EPIC study HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancer.…”

Section: Epidemiologymentioning

confidence: 62%

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Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

et al. 2014

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To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed‐up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV‐2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2–2.0) and 1.8 (1.1–2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4–2.4) and 7.4 (2.8–19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9–1.9) and 2.3 (1.3–4.1) for CT seropositivity, and 1.4 (1.0–2.0) and 1.5 (0.9–2.6) for HHV‐2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR = 10.2 (3.3–31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non‐STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV‐2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development.

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Section: Epidemiologysupporting

confidence: 92%

Section: Epidemiologymentioning

confidence: 62%

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

et al. 2014

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“…According to the present results, the application of E6/E7 protein detection in CC screening could reduce the limitations of other recent technologies, such as the Pap test and HC2 test, and the indicators (E6/E7 proteins) for both cervical pre-cancer and progression to CC could be quantified with the standard detection method established in the present study (17,21). However, not all types of anti-E6/E7 monoclonal antibodies exhibit high specificity currently (8,38). Therefore, further studies about the combination of E6/E7 mRNA and protein testing may be introduced to improve the specificity and sensitivity of CC screening.…”

Section: Discussionmentioning

confidence: 65%

“…However, due to the low sensitivity of the aforementioned methods, females with high risk of developing CC require regular re-tests to confirm the accuracy of the results (7). Among patients with negative cytology results but positive HPV DNA test results, a small percentage will develop CC (8). Therefore, an efficient diagnostic method is required for these particular patients (TCT -/HPV + ).…”

Section: Introductionmentioning

confidence: 99%

E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre‑cancerous lesions and cervical cancer in a Chinese population

Shi

Líu

et al. 2017

Oncol Lett

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Abstract. The present prospective study aimed to evaluate the effects of E6/E7 protein detection by western blotting on cervical cancer (CC) early screening compared with detection by Hybrid Capture 2 (HC2) test and ThinPrep cytological test (TCT) in a Chinese population. A total of 450 cases of cervical intraepithelial neoplasia (CIN) suspected samples (positive in ≥1 indicator of TCT and HC2 test) were recruited from women who were treated at the International Peace Maternity and Child Health Hospital (Shanghai, China) from March 2014 to February 2015. Each sample was analyzed by cytological test. In addition, human papillomavirus (HPV) DNA examination by Hybrid Capture Tube test and E6/E7 protein expression detection by western blotting were performed in all samples, as well as histologic diagnosis to determine the stage of CIN. The results revealed that, for the diagnosis of CIN2 + , although the sensitivity of E6/E7 protein detection was lower than that of HC2 test (71.3 vs. 96.6%, respectively), the specificity was markedly improved (67.6 vs. 5.9%, respectively). Compared with that of TCT, the sensitivity of E6/E7 protein detection was much higher (36.2 vs. 71.3%, respectively), but the specificity was lower (88.2 vs. 67.6%, respectively). In the present study, HPV E6/E7 protein expression was evaluated as a potential new biomarker for CC, with satisfactory diagnostic values for HPV types 16 and 18. The relative diagnostic value may be further improved by combination of E6/E7 messenger RNA detection.

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“…An increased T-cell response against HPV E7 epitopes has been detected in the blood of patients with HPV-positive HNSCC. [13][14][15] A more recent study has shown that T cells that proliferate and synthesize inflammatory cytokines upon HPV16 E6 and E7 oncoprotein recognition can be isolated from OSCC biopsies or tumor-draining lymph nodes. 16 Lymphocyte infiltration and expression of lymphocyte markers have been correlated with improved prognosis of patients with HNSCC.…”

mentioning

confidence: 99%

CD8‐alpha T‐cell infiltration in human papillomavirus‐related oropharyngeal carcinoma correlates with improved patient prognosis

Jung

Guihard²,

Krugell³

et al. 2012

Intl Journal of Cancer

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Patients with human papillomavirus (HPV)-related oropharyngeal tumors display improved prognosis. The biological basis of this tumor phenotype is poorly understood. We investigated whether increased lymphocyte infiltrate in HPV-positive oropharyngeal squamous cell carcinomas could account for better prognosis. We previously identified, in an Affymetrix GeneChip analysis of 83 HPV-unrelated and 11 HPV-related squamous cell carcinoma of the oropharynx, several candidate genes, including CD8a and CD3f. Their expression was validated in this study by qRT-PCR on an independent clinical series of 144 oropharyngeal tumors. Immunohistochemical staining of tumor specimens was performed to evaluate infiltration of tumor stroma by CD81 and CD41 lymphocytes. The prognostic value of CD8a and CD3f expression levels was measured by Kaplan-Meier and Cox regression model analyses. Immune response-related signaling pathways were found to be deregulated in HPV-positive oropharyngeal tumors. Expression of CD8a, CD3f, granzyme K, CD28 and integrin aL RNAs was upregulated in HPV-positive lesions when compared with HPV-unrelated tumors (p < 0.05). Stroma of HPV-positive tumors was frequently and strongly infiltrated by CD8a-and CD3f-positive T cells. CD8a RNA expression correlated with both improved global (Kaplan-Meier; p 5 0.005; Cox regression: p 5 0.003) and disease-free (Cox regression: p 5 0.04) survival. CD3f RNA expression correlated with improved overall survival (Cox regression: p 5 0.024). These results suggest that an increased cytotoxic T-cell-based antitumor immune response is involved in improved prognosis of patients with HPV-positive tumors.The presence of human papillomaviruses (HPVs; mainly HPV type 16) correlates with the onset and development of about 25% of head and neck squamous cell carcinomas (HNSCC). 1 HPV-positive cancers of the head and neck arise mainly in the oropharynx and define a subgroup of radioand chemosensitive tumors with distinct clinical, pathological and molecular features and improved prognosis with respect to their HPV-negative counterparts. [2][3][4][5] The majority of HPVrelated oropharyngeal squamous cell carcinomas (OSCC) express wild-type TP53, 6,7 which might be involved in the improved response of tumors to treatment. Despite thorough analysis of gene expression profiles of HPV-positive OSCC by several groups, [8][9][10][11] no novel prognostic or predictive biomarker has been identified, and the molecular mechanisms that underlie improved prognosis of HPV-related OSCC are poorly understood.The immune response has an important impact in many HPV-associated tumors and can have either favorable or unfavorable consequences. 12 The importance of the immune response in HPV-related OSCC is less well established. An increased T-cell response against HPV E7 epitopes has been detected in the blood of patients with HPV-positive HNSCC. 13-15 A more recent study has shown that T cells that proliferate and synthesize inflammatory cytokines upon HPV16 E6 and E7 oncoprotein recognition can be isolate...

show abstract

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia

Cited by 60 publications

References 24 publications

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre‑cancerous lesions and cervical cancer in a Chinese population

CD8‐alpha T‐cell infiltration in human papillomavirus‐related oropharyngeal carcinoma correlates with improved patient prognosis

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