Infectious Agents and Cancer最新文献

Background: Although anal cancer is a rare malignancy, its incidence is up to 30 times higher among individuals living with HIV. Recent evidence suggests that Highly Active Antiretroviral Therapy (HAART) regimens containing sulfonyl groups may exhibit antitumor properties. Based on these findings, we hypothesize that HAART regimens incorporating sulfonyl-containing compounds could influence oncologic outcomes in HIV-positive patients undergoing definitive chemoradiotherapy (CRT) for anal cancer.

Methods: From a cohort of 537 patients with stage I-III invasive anal cancer treated between August 2010 and April 2022, 56 HIV-positive patients who underwent definitive chemoradiotherapy were included in the analysis. .

Results: Most patients were male. The mean age was 52 years in the non-sulfonyl-HAART group and 53 years in the sulfonyl-HAART group. The mean CD4 count was significantly higher in the non-sulfonyl group compared to the sulfonyl group (523 vs. 287 cells/mm³, p = 0.02). Grade 3-4 toxicities occurred in 60% and 38% of patients, respectively (p = 0.18). Chemotherapy dose reductions were required in 10% of the non-sulfonyl group and 8% of the sulfonyl group (p = 1.0). Treatment discontinuation during chemoradiotherapy occurred in 17% vs. 23% of patients, respectively (p = 0.7). The overall response rate at 6 months post-treatment was significantly higher in the sulfonyl-HAART group (100%) compared to the non-sulfonyl group (20/36; 55.6%), Odds Ratio (OR) 0.00, 95% CI: 0-0.72, p = 0.004). After adjustment, CD4 count was not associated with treatment response (logistic regression OR: 1.00; 95% CI: 0.99- 1.00, p = 0.3). The median progression-free survival (PFS) in the non-sulfonyl-HAART group was 70 months (p = 0.45), and overall survival (OS) was similar between groups (p = 0.6); the median OS was not reached in the sulfonyl-HAART group. In the Cox proportional hazards model, age, clinical stage, and lack of response to CRT at 6 months were independent predictors of worse survival. ( CONCLUSION: HIV-positive patients with anal cancer who received sulfonyl-containing HAART during definitive chemoradiotherapy demonstrated a significantly higher overall response rate at 6 months, independent of baseline CD4 count. However, no significant differences were observed between the sulfonyl and non-sulfonyl groups in terms of treatment-related toxicities, treatment discontinuation, progression-free survival, or overall survival.

Background: Human papillomavirus (HPV) is the major causative agent of genital warts and various anogenital cancers. In Vietnam, limited data exists on HPV genotype prevalence and distribution. This study aimed to determine the prevalence and distribution of HPV types among patients with genital warts in Can Tho City and to explore their associations with demographic and clinical characteristics.

Methods: A cross-sectional study was conducted at Can Tho Dermatology Hospital with 109 patients diagnosed with genital warts. HPV genotyping was performed using real-time PCR and reverse dot blot hybridization to detect both the low- and high-risk HPV types. Associations between HPV types and variables such as age, sex, and lesion site were analyzed statistically.

Results: HPV was detected in 89% of the patients. The low-risk types HPV11 (50.5%) and HPV6 (47.4%) were the most common. The high-risk types, HPV51 (30.9%) and HPV52 (20.6%), were frequent, especially in females (83.6% vs. 63.3% in males, p = 0.030). Co-infections occurred in 71.6% of females and 60% of males. Lesion location correlated with HPV type distribution.

Conclusions: The high prevalence of both low- and high-risk HPV types highlights the need for enhanced vaccination coverage and continued HPV surveillance. These findings provide critical data for developing HPV prevention strategies in Vietnam.

Objective: Breast cancer (BC) poses a significant global health challenge, and its potential link to HPV warrants investigation. This study investigates the prevalence, genotype distribution, and clinicopathological associations of human papillomavirus (HPV) in breast cancer patients from Pakistan.

Methods: This single-institutional cross-sectional study included 501 FFPE BC specimens from female patients and 110 benign controls, collected between January 2019 and December 2023. High-risk (HR) HPV DNA was detected via highly sensitive real-time PCR, with genotyping conducted using the INNO-LiPA Genotyping Extra II assay. Clinicopathological data, including tumor grade, size, lymph node metastasis, and receptor status, were analyzed for associations with HPV infection. Statistical analyses employed the Kruskal-Wallis test for continuous variables and Fisher's exact or chi-square tests for categorical variables, as appropriate (p < 0.05).

Results: HPV DNA was detected in 10.5% of BC cases (n = 53/501) compared to other statuses, with HR genotypes predominating (91%). HPV-16 (26%) and HPV-18 (15%) were the most frequent genotypes. HPV-positive cases exhibited aggressive tumor characteristics, including 58.5% grade III tumors, a mean tumor size of 65.6 ± 46.4 mm, and 32.1% N3 disease, with an increasing prevalence of HR-HPV associated with tumor stage and significance (p < 0.05). Invasive ductal carcinoma (34%) and invasive lobular carcinoma (28.3%) were the most common histological subtypes. Metaplastic carcinomas, with the largest mean tumor size (86.4 ± 74.6 mm), showed the highest HPV-16 prevalence (28.6%) and were linked to HR-HPV infection. Peak HPV incidence occurred in patients aged 51-60 years (37.7%). Geographically, HPV-16 predominated in Lahore (50%) and Peshawar (60%).

Conclusion: This study links HR-HPV to aggressive BC, with HPV-16 and -18 predominating in urban areas. Additionally, it highlights the importance of targeted vaccination and research into subtype-specific oncogenesis.

Background: Users of intrauterine devices (IUDs) have been found to have a lower incidence of cervical cancer in meta-analyses, but these studies have not been able to examine the influence of IUD type. The aim of this study is to investigate the incidence of de novo high-risk human papillomavirus (HPV) infections in relation to the reported use of contraceptive methods, with special regard to different types of IUDs.

Methods: A sample of participants in the national screening program for cervical cancer (n = 11,702) with a negative HPV test in 2017-2018 were included. Their subsequent HPV test results in 2020-2023 were analyzed in relation to their reported contraceptive method.

Results: Participants who reported use of hormonal contraception had higher incidence of a positive HPV screening test (5.6%) compared with women with no reported contraception (4.2%) (OR 1.29; 95% CI 1.01-1.64). There was no significant difference in HPV incidence among women who reported use of hormonal IUD (HIUD) or copper-containing IUD (CU-IUD). Women who reported use of the same contraceptive method in both screening rounds showed no significant differences in HPV incidence, regardless of the contraceptive method they had used.

Conclusion: The incidence of de novo HPV infections is not significantly different in users of different types of IUD.

Oropharyngeal squamous cell carcinoma (OPSCC), a type of head and neck cancer (HNC), represents a major global health issue contributing to substantial morbidity and mortality. Human papillomavirus (HPV) is an established oncogenic virus and is among the major causes for OPSCC. Although HPV has been identified as a risk factor for oral squamous cell carcinoma (OSCC). Limited information exists on its current prevalence and associated risk factors in India.The current research aimed to detect different high-risk HPV genotypes among OSCC and OPSCC patients attending a tertiary care hospital in Mangalore, India. After consenting to participate in the study, tumor tissue biopsies were collected from 25 oral cancer patients. Nucleic acid was extracted from samples and tested for high-risk HPV by real-time PCR and conventional multiplex PCR. Furthermore, Sanger sequencing and bioinformatic analysis were performed to identify the specific genotypes. Among the 25 biopsy samples tested, three samples (12%) were positive for high-risk HPV. The sequencing results indicated that two of the samples belonged to HR HPV type 58, and one belonged to type 59. Clinical analysis revealed a significant association between HPV-positive OSCC and high alcohol consumption and tobacco chewing.The findings of the present study suggest that in addition to traditional risk factors such as alcohol and tobacco use, HPV may also be a risk factor for the development and progression of OSCC, although its specific etiological role remains unclear. While most Indian studies have consistently reported HPV 16 and 18 as the predominant subtypes, our findings highlight the presence of other HR-HPV types 58 and 59 among OSCC patients.

Cancer research is constantly evolving to yield successful innovations. A plethora of pre-clinical studies have illustrated the promising potential utility of parasites and parasite-derived molecules in cancer therapy. In this review, we underscore, for the first time, the possible multifaceted applications of parasites in the field of oncology, aiming to draw attention to the vital role of parasite-derived cancer therapy and offer novel insights for the evolution of advanced cancer therapeutics. Several studies have demonstrated that parasites offer a variety of strategies for cancer therapy. These include acting as immunotherapeutics such as cancer vaccines, therapeutic antibodies, adjuvants, immunomodulators, oncolytic agents, and NF-κB inhibitors. Additionally, they can be utilized in targeted therapy, gene therapy, and in combination with current cancer treatments to synergistically enhance their effectiveness. A notable strategy is parasites' ability to overcome tumor resistance to chemotherapy, a significant obstacle in cancer therapy. There is still much to explore about parasite-based anti-cancer therapies. With further research and the translation of parasitological discoveries into effective cancer interventions, parasites may hold the key to effectively treat cancer in the near future.

Background: Development of immunotherapies and vaccines to treat HPV16-associated cancer requires reliable/effective small animal models. We developed such a model based on the murine mammary gland adenocarcinoma cells engineered to express HPV16 oncoproteins E6 and E7, and used it to assess the protective and therapeutic potential of E6/E7-based DNA-immunogens.

Methods: 4T1luc2 subclones with single genomic inserts of HPV16 E6/E7 DNA (B2, H6) were obtained by lentiviral transduction. DNA-immunogens were designed encoding expression-optimized consensus HPV16 E6 and E7 mutated to disrupt p53- and Rb-binding, both controlled by the human elongation factor 1a promoter. In prophylactic settings, BALB/c mice received E6, E7, E6/E7 DNA or vector, followed by challenge with B2 or H6 cells, and in therapeutic settings, were challenged with B2 or H6 cells, and DNA-immunized with E6 or vector. In reference series, C57bl/6 mice were challenged with TC1/luc2 cells and DNA-immunized with E6, E7, or E6/E7, or vector DNA. Tumor growth was monitored morphometrically and by in vivo bioluminescence imaging (BLI); metastatic activity, by ex vivo organ BLI, PCR and histology, and in vitro cytokine production by T-cells of immunized mice, by flow cytometry.

Results: E6/E7-expressing 4T1luc2 subclones B2 and H6 longitudinally expressed mRNA of E7 and of E6*I, E6*II, full length E6 (E6FL) isoforms. The levels of expression of E6 and E7 mRNA significantly increased with time. In naïve mice, B2 and H6 generated solid tumors with lung metastases. B2 and H6 cells were used to assess the efficacy of prophylactic DNA-immunization with E6 and E7. In immunogenicity tests, E6 DNA recipients developed Th1-type T-cell response, their unstimulated T-cells produced IFN-γ and IL-2. E7 DNA was nonimmunogenic, while unstimulated T-cells produced TNF-α. In prophylactic settings, DNA-immunization with E6 and E7 suppressed formation of B2/H6 tumors. In therapeutic settings, DNA-immunization with E6 (not E7) restricted growth of TC-1/luc2 tumors, but had no effect on tumorigenic or metastatic activity of E6/E7-expressing 4T1luc2 cells. In both TC-1/luc2 and 4T1luc2E6/E7-models, E7 DNA recipients developed systemic inflammation manifested by enhanced formation of microgranulomas in the liver.

Conclusions: 4T1luc2 cells stably expressing HPV16 E6/E7 present an attractive alternative to TC-1 model allowing stringent assessment of both protective and therapeutic potential of E6/E7-based vaccines in BALB/c mice.

We have previously reported that microorganism-associated antigens (MAAs) share high sequence and conformational homology with tumor-associated antigens (TAAs) as well as T cells cross-react with homologous MAA/TAA pairs. More recently, we have also shown that the SARS-CoV-2 preventive vaccine, besides the humoral response, is able to elicit also a T cell response which cross-react with homologous TAAs. In the present study we analyzed the mandatory pediatric vaccines, namely the hexavalent vaccine (Diphtheria, Tetanus, Pertussis (whooping cough), Polio, Haemophilus influenzae type b (Hib), Hepatitis B) and the MMR (measles, mumps and rubella), and the chickenpox vaccine. MHC class I epitopes (9 mers) from each of these vaccines were predicted for the most frequent 12 HLA A and B alleles. Overall, 3177 strong binders (SBs) were identified and the most frequently associated allele is the HLA-A*02:01. Of these, 397 are predicted for the hexavalent vaccine and 571 in the MMR vaccine. A molecular mimicry with 59 SBs derived from cellular proteins has been identified and 13 of these proteins are significantly overexpressed in several human cancers. All these results strongly suggest that the mandatory pediatric vaccinations may potentially elicit a CD8⁺ T cell response against several microbial epitopes in individuals with different genetic background. Such microbial epitopes show high homology with epitopes from cellular proteins overexpressed in multiple cancer types. Therefore, a potential anti-microbial CD8⁺ T cell response may cross-react against cancer cells. This would imply that the pediatric vaccinations may be a preventive measure against both microbial infections and a broad spectrum of tumors. A large-scale immune-epidemiological study will be needed to confirm the proposed suggestive results.

Cervical cancer is one of the leading causes of cancer-related death among women worldwide, and high-risk human papillomavirus (HR-HPV) plays a crucial role in its development. HPV's oncogenic processes include the viral oncoproteins E6 and E7, which interfere with essential biological processes, causing DNA instability and uncontrolled cell growth. Recent research suggests that microRNAs (miRNAs) have a role in HPV-mediated tumor development, with dysregulation of particular miRNAs influencing cancer cell proliferation, immune escape, and therapy resistance. This review summarizes the most recent research on HPV's molecular interactions with host miRNAs, focusing on their functions in regulating tumor-suppressive genes and oncogenic mechanisms. Furthermore, we investigate HPV-induced epigenetic alterations that contribute to miRNA dysregulation and corresponding changes in cell cycle control, apoptosis, and metastasis. Discovering these molecular interactions provides fresh insights into personalized medicine techniques for CC detection and therapy.

The significance of viral load from high-risk human papillomavirus (HR-HPV) in the detection of cervical lesions is still debated. This study aims to assess the correlation between the viral load of the most common high-risk genotypes (HPV16, HPV18, HPV52, HPV53, HPV58, and HPV68) and cervical lesions in South China, and to ascertain the role of specific HPV viral load types as potential diagnostic biomarkers for cervical lesions. The study included 1787 patients, with HPV types and viral load measured by fluorescent PCR method. The relationship between viral load and cervical lesions was analyzed through both linear and non-linear methods. Viral loads of HPV 16/18/52/58 are risk factors for the occurrence of cervical lesions, Notably, HPV16 and HPV58 respectively demonstrated a non-linear association with the emergence of CIN1 + and CIN2 + cervical lesions, indicating that HPV viral load may serve as a stratification marker for recognizing heightened risk of cervical lesions, thus enhancing risk stratification in cervical cancer screening.