Immune responses to human papillomavirus in genital tract of women with cervical cancer

Nguyen, Huan Huu; Broker, Thomas R.; Chow, Louise T.; Alvarez, Ronald D.; Vu, Huong; Andrasi, Judit; Brewer, Lorie R.; Jin, Ge; Městecký, Jiří

doi:10.1016/j.ygyno.2004.10.019

Cited by 57 publications

(55 citation statements)

References 59 publications

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“…These findings could not be explained by the presence of endocervical infections such as C. trachomatis or N. gonorrhoeae since these were excluded from our analysis. Nguyen et al previously reported a similar observation (12), with high levels of IL-1␤, IL-6, and IL-8 but low or undetectable levels of other cytokines, by use of a multiplex immunoassay, in vaginal washes from patients with and those without cervical cancer. The ready detection of these proinflammatory cytokines in cervical secretions may be reflective of the female reproductive tract as an anatomic site that is constantly exposed to immunogenic stimulation.…”

Section: Discussionsupporting

confidence: 58%

“…Recently introduced multiplex, suspension-array-based immunoassay methods, such as the Luminex xMAP system, provide a novel platform for the detection of multiple analytes in small volumes (18). Although this technology has been used to measure cytokines in vaginal washes in women with cancer (12) and cervical swabs in pregnant women (17), comparisons between studies can be challenging due to differing specimen collection and recovery methods.…”

mentioning

confidence: 99%

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Determination of Cytokine Protein Levels in Cervical Mucus Samples from Young Women by a Multiplex Immunoassay Method and Assessment of Correlates

Lieberman

Moscicki

Sumerel³

et al. 2008

Clin Vaccine Immunol

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Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels. We used a multiplex, suspension-array-based immunoassay method to measure 10 proinflammatory (interleukin-1␤ [IL-1␤], IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-␥], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens collected via ophthalmic sponge from 72 healthy, nonpregnant women and correlate their levels with biologic and behavioral covariates in a cross-sectional design. Proinflammatory and immunoregulatory cytokines were readily detected, although proinflammatory cytokines were present at markedly higher levels than were immunoregulatory cytokines. Among the covariates examined, the most striking finding was the significant (P < 0.05) association between depressed levels of the cytokines IFN-␥, IL-1␤, IL-6, and IL-10 and cigarette smoking. Also, nonsignificant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomic site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.A complex interplay of systemic and local immune responses limits the anatomic extent and influences the natural history of sexually transmitted infections of the cervix. At the local level, the study of these responses often includes characterization of the local cytokine milieu. With the microbiologic complexity of the cervical environment, it is likely that numerous cytokines are locally expressed and essential for the proper control of pathogens. Castle et al. showed that cervical concentrations of cytokines do not correlate with plasma concentrations (3), emphasizing the need to examine the mucosal component of the host response using appropriate specimen types.Clearly, the choice of specimen type is influenced by the immune compartment in question and is often limited by the amount of sample available. The cervix is unique in that it naturally produces cervical secretions by columnar cells, and these secretions appear to be rich in immunoregulatory proteins including cytokines. Various tools for collecting cervical secretions in an undiluted form have been tested; all result in small sample volumes, thus limiting the number of immune markers that can be tested. While enzyme-linked immunosorbent assays have been used to measure up to six markers in secretions, this method is not feasible to measure greater numbers of analytes in small-volume secretions (2). Recently introduced multiplex, suspension-array-based immunoassay methods, such as the Luminex xMAP system, provide a novel platform for the detection of mult...

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

Determination of Cytokine Protein Levels in Cervical Mucus Samples from Young Women by a Multiplex Immunoassay Method and Assessment of Correlates

Lieberman

Moscicki

Sumerel³

et al. 2008

Clin Vaccine Immunol

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“…Several mechanisms have been proposed to explain the immunomodulatory effects of HLA-G in cancer. HLA-G may induce Th2 cytokine (IL-4, IL-5, IL-10) polarization, which is not effective on viral depletion (Nakanishi et al 2001), permitting viral maintenance and lesion progression (Clerici et al 1997;Nguyen et al 2005). In our findings, low expression of HLA-G in cervical invasive lesions was observed, as demonstrated in Goncalves et al (2008).…”

Section: Discussioncontrasting

confidence: 50%

Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

Guimarães

Soares

Donadi

et al. 2009

J Histochem Cytochem.

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S U M M A R Y Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma ( Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies. (J Histochem Cytochem 58:405-411, 2010)

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“…Moreover, antibody responses are detected in early phases of infection [39][40][41], as well as in patients with cervical carcinoma [42,43]. In this regard, other types of immune cells may also be of importance.…”

Section: Discussionmentioning

confidence: 99%

“…Data obtained in each analysis were processed automatically by the system. CLART ® HPV 2 kit allowed the detection of infection and coinfection of 35 different HPV genotypes, namely 6,11,16,18,26,31,33,35,39,40,42,43,44,45,51,52,53,54,56,58,59,61,62,66,68,70,71,72,73,81,82,83,84, 85 and 89 [24]. Diagnostic sensitivity and specificity of the CLART ® HPV 2 kit amount to 98.2% and 100% respectively, according to the manufacturer.…”

Section: Hpv Genotypingmentioning

confidence: 99%

B-lymphocyte, Macrophage and Mast Cell Density in the Stroma Underlying HPV-Related Cervical Squamous Epithelial Lesions and their Relationship to Disease Severity: an Immunohistochemical Study

Foukas¹,

Zourla²,

Tsiodras³

et al. 2012

J Clinic Experiment Pathol

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Immune responses to human papillomavirus in genital tract of women with cervical cancer

Cited by 57 publications

References 59 publications

Determination of Cytokine Protein Levels in Cervical Mucus Samples from Young Women by a Multiplex Immunoassay Method and Assessment of Correlates

Determination of Cytokine Protein Levels in Cervical Mucus Samples from Young Women by a Multiplex Immunoassay Method and Assessment of Correlates

Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

B-lymphocyte, Macrophage and Mast Cell Density in the Stroma Underlying HPV-Related Cervical Squamous Epithelial Lesions and their Relationship to Disease Severity: an Immunohistochemical Study

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