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Immunologic treatments for precancerous lesions and uterine cervical cancer.

ABSTRACT: Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem.

SUBMITTER: Vici P

PROVIDER: S-EPMC3986944 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Immunologic treatments for precancerous lesions and uterine cervical cancer.

Vici Patrizia P Mariani Luciano L Pizzuti Laura L Sergi Domenico D Di Lauro Luigi L Vizza Enrico E Tomao Federica F Tomao Silverio S Cavallotti Claudia C Paolini Francesca F Venuti Aldo A

Journal of experimental & clinical cancer research : CR 20140326

Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytoki ...[more]

PMID: 24667138

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Project description:OBJECTIVE:To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS:Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS:Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS:We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Project description:BackgroundSince the mid-1990 s, there have been growing efforts to prevent cervical cancer in less-developed countries through the development of innovative screening approaches such as visual inspection of the cervix associated with same day management of cervical lesions with cryotherapy or loop electrosurgical excision procedure (LEEP). In the past, promising cancer screening interventions have been widely promoted despite incomplete evidence, only to become the subject of intense controversies about ensuing net health benefit. Because the efficacy and effectiveness of the new protocols for global cervical cancer screening have not been well characterized yet, and as a contribution to the evaluation of the balance between the benefits and risks of these protocols, we reviewed the literature on the safety of cryotherapy and LEEP for cervical intraepithelial neoplasia (CIN) in low- and middle-income countries.MethodsWe searched 12 databases (Medline, Google Scholar, Scopus, Cochrane Library, Web of Science, OCLC, PAIS International Database, WHO Global Health Library, CINAHL, Science.gov, NYAM Grey Literature Report, and POPLINE) for original research published between January 1995 and April 2009. Both peer-reviewed publications and items of "grey" literature were retrieved; no language restriction was applied. We calculated the median (minimum, maximum) reported rate for each harm considered. Because of limitations and heterogeneity in the data, no formal meta-analysis was performed.ResultsThe search identified 32 articles that reported safety data from 24 cryotherapy and LEEP studies. The combined sample consisted of 6,902 women treated by cryotherapy and 4,524 women treated by LEEP. Most studies were conducted in reference or research settings in Asia and Africa. Short-term harms of cryotherapy and LEEP appeared to be similar to those described in the literature from high-income countries. Information was sparse on HIV-related harms and long-term reproductive outcomes of treatment.ConclusionsWhen performed in resource-limited settings by qualified providers, cryotherapy and LEEP are not associated with excess harm. However, available data are insufficient to propose fully evidence-based protocols for routine screening of HIV-infected women and women of reproductive age.

Project description:The objectives of this study were to identify the associated factors with cancerous and precancerous lesions of cervix. In Africa, the incidence of uterine cervical neoplasms varies from one region to another, where most women with uterine cervical neoplasms are seen at an advanced stage. For this reason, uterine cervical neoplasms mass screening reduces the incidence and mortality due to this disease, similar to what is being done in Europe. A cross-sectional analytical study was conducted. Socio-demographic characteristics, gynaecological-obstetrical history, risk factors, data from visual inspection with acetic acid and visual inspection with Lugol, colposcopy impressions and results of cytological analysis were performed. A simple and multiple regression were performed to establish a statistically significant difference between certain factors and the presence of precancerous or cancerous lesions of uterine cervical. In this study, of 63 women diagnosed histologically, 43 had precancerous lesions and 20 had cancerous lesions. we found that being older than 35, having the first intercourse before 18, having an antecedent of STI, being a widow and using of tobacco were risk factors associated with precancerous lesions (p = 0.013 with OR = 3.44 (1.22-9.73), p = 0.009 with OR = 4.07 (1.69-13.08), p < 0.001 with OR = 3.80 (1.94-7.47), p < 0.001 with OR = 9.77 (3.87-24.70) and p < 0.001 with OR = 5.47 (2.60-11.52)) respectively. Only being older than 45, being a widow and using tobacco were risk factors associated with cancerous lesions (p = 0.021 with OR = 2.01 (1.58-3.56), p = 0.02 with OR = 2.96 (2.10-3.87), p = 0.041 with OR = 1.98 (1.46-2.44)) respectively. Among participants diagnosed with uterine cervical neoplasms, there was a significant association with the STI, marital status and smoking. Despite the integration of the detection of precancerous uterine cervical neoplasms lesions into health facilities in Gabon, uterine cervical neoplasms ranks second among women's cancers in terms of incidence and first in terms of mortality.

Project description:Cervical cancer is the second most prevalent cancer among women in the developing countries including Ethiopia. Precancerous lesions can be developed and risk to the development of cervical cancer over time. Early identification of the precancerous lesion and its risk factor is paramount in preventing cervical cancer. However, the determinants of cervical precancerous lesions are not well documented in Ethiopia. Therefore, this study is conducted to determine factors associated with cervical precancerous lesion among women screened for cervical cancer.A hospital-based unmatched case-control study was conducted in selected health facilities in Addis Ababa from March to April 2016. Data were collected from 114 cases and 229 controls using an interviewer-administered questionnaire, entered to Epi Info version 7, and exported to SPSS version 20 for analysis. Odds ratios with its 95% confidence intervals and two-tailed P-value were calculated. Variables with P-value ? 0.2 in the bivariate analysis were included in the multivariate logistic regression model.Women aged 40-49 years had 2.4-fold higher odds of precancerous lesions compared to those aged 30-39 (Adjusted Odds Ratio = 2.4, 95% Confidence Interval: 1.27-4.54). Women having history of sexually transmitted infections were significantly associated with cervical precancerous lesion compared to their counterparts (Adjusted Odds Ratio = 3.20, 95% Confidence Interval: 1.26-8.10). Similarly, those women who had two or more lifetime sexual partners (Adjusted Odds Ratio = 2.17 95% Confidence Interval: 1.01-4.67), and women whose husbands had two or more lifetime sexual partners (Adjusted Odds Ratio = 3.03, 95% Confidence Interval: 1.25, 7.33) had higher odds of cervical precancerous lesions.Older age, history of multiple sexual partners and sexual transmitted infections were associated with increased risk of precancerous lesion. Therefore, women with higher risk of precancerous lesions should be encouraged to be screened more frequently for cervical cancer.

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Immunologic treatments for precancerous lesions and uterine cervical cancer.

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Immunologic treatments for precancerous lesions and uterine cervical cancer.

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