Infectious Agents and Cancer最新文献

Background: Women Living with HIV (WLHIV) are at increased risk of persistent high-risk Human Papillomavirus (HR-HPV) infections and cervical cancer. However, data on HPV genotype distribution and cervical cytologic abnormalities remain limited in North Africa, particularly among women receiving effective antiretroviral therapy (ART).

Objective: To assess the frequency of cytologic abnormalities in WLHIV in Sétif, Algeria, identify HR-HPV genotypes, and evaluate associated immunovirological factors.

Methods: A cross-sectional study was conducted from January to December 2024 at the HIV/STI/AIDS Reference Center in Sétif. WLHIV aged ≥ 18 years who provided informed consent were included. Each participant underwent a gynecological examination, cervical cytology (Pap smear), HR-HPV genotyping by molecular biology, and immunovirological assessment (CD4 T-cell count, HIV viral load). Colposcopy and biopsy were performed when indicated.

Results: Among 115 enrolled participants, 100 smears were interpretable. Cytologic abnormalities : Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-Grade/High-Grade Squamous Intraepithelial Lesions LSIL, HSIL) were found in 28% of WLHIV. HR-HPV infection was detected in 32% of participants, mainly genotypes HPV52, HPV16, and HPV18. A significant association was observed between HR-HPV positivity and high-grade lesions (HSIL) (p = 0.018; OR = 9.57, 95% CI: 1.02-89.48).

Conclusion: WLHIV in Algeria show a high prevalence of HPV-related cytologic abnormalities, even with adequate immune status and viral suppression. These findings emphasize the importance of regular cervical screening and support current global recommendations for comprehensive prevention strategies, including HPV testing and vaccination.

Background: In cervical screening, human papillomavirus (HPV)-positive women at 1-year retesting are typically referred to colposcopy. This study, by the use of extended genotyping, estimates the impact of distinguishing persistent from new infections in an effort to reduce colposcopy referral. It also evaluates whether the new infection rate varies according to genotyping, cytology, p16/ki67, and E6/E7 mRNA results.

Methods: We analyzed data from HPV-DNA-positive women at baseline in the NTCC2 trial genotyped with the Onclarity HPV assay. Eligible participants were Onclarity-positive women without baseline CIN2+ who had a cervicovaginal sample collected at least 10 months after baseline. Persistent infections were defined as cases with at least one common genotype between baseline and follow-up specimens. New infections were defined as cases positive for different genotypes at follow-up, with no baseline genotypes detected.

Results: Among 1,540 women included, 613 were Onclarity-positive at both baseline and 1-year retesting: 488 (79.6%) had persistent infections, while 68 (11.1%) had new ones. All the 11 CIN3 cases identified at follow-up occurred in women with persistent infections. The new infection rate was significantly higher in women with baseline single-channel compared to multiple channels positivity (13.3% vs 5.5%, p=0.001). Stratifying by age, persistence and new infection rates were significantly different among different age groups (respectively p=0.005 and p=0.009). No significant difference in both new infections and persistence rate was observed between baseline cytology positive and negative cases. Stratifying by baseline p16/ki67 results, we found a significantly higher rate of persistent cases among p16/ki67 positive cases and of new infections among p16/ki67 negative cases (respectively p=0.013 and p=0.016). E6/E7 mRNA findings affected only persistence rate showing a significant difference in the proportion of persistent cases between positive and negative cases (p=0.004), but did not affect new infection rate.

Conclusion: Extended genotyping classified 11.5% of 1-year HPV-positive cases as new infections. As 1-year HPV positivity accounts for about 60% of first-level colposcopies, this corresponds to about 7% of colposcopies. Baseline single-channel positivity, age, and p16/ki67-negative results may influence this proportion.

Trial registration: Clinicaltrials.gov registration number: NCT01837693, New Technology in Cervical Cancer 2 (NTCC2) study.

Objective: To investigate the oncogenic risks of distinct high-risk human papillomavirus (HR-HPV) genotypes and whether multiple infections exacerbate pathogenicity, with analysis of age stratification and viral load impact.

Methods: Clinical and pathological data from 2,525 patients undergoing colposcopy-directed biopsy for cervical abnormalities (2020-2023) were analyzed. HPV genotyping (18 types) and viral load quantification (Ct-values) were performed using PCR-membrane hybridization. Histopathology (CC/LSIL/HSIL/SCC) was evaluated by blinded experts. Statistical analyses included age stratification (< 35 vs. ≥35 years) and multivariate adjustment for viral load (Ct ≤ 30).

Result: HR-HPV single-type infections predominated (1,774 cases, 70.26%), with genotype distribution: 16 (17.98%), 52 (10.50%), 58 (7.88%), 53 (4.63%), and 18 (4.55%). Multiple infections occurred in 474 cases (18.77%). Versus HPV-negative/low-risk controls, the highest pathogenic risks were: type 16 (OR = 7.96, 95% CI:5.41-11.71), type 58 (OR = 5.80, 95% CI:3.75-8.99), multiple infections (OR = 5.02, 95% CI:3.42-7.37), type 18 (OR = 4.86, 95% CI:2.95-8.02), and type 35 (OR = 4.07, 95% CI:1.82-9.10) (all P = 0.001). Age ≥ 35 years independently increased HSIL + risk (OR = 2.16, 95% CI:1.62-2.88, P = 0.001), with HPV16/18/35 showing significantly higher ORs in this group. High viral load (Ct ≤ 30) independently predicted HSIL + progression (OR = 2.98, 95% CI:1.92-4.63, P = 0.001). Multiple infections did not increase risk for genotypes 16/18/33/35/52/56/58/68 versus single infections, except for HPV51 (P = 0.01).

Conclusion: Genotype 16 demonstrates the strongest oncogenic potential, with pathogenic hierarchy: 16 > 58 > 18 > 35. Multiple infections do not synergistically increase risk for dominant genotypes. Age ≥ 35 years and high viral load (Ct ≤ 30) independently elevate cervical lesion severity, supporting their integration into risk-stratified screening protocols.

Clinical trial number: Not applicable.

Background: Kaposi sarcoma (KS) is an angioproliferative tumor caused by human herpesvirus 8 and is an AIDS-defining illness. Combination antiretroviral therapy (ART) was introduced in the United States in 1996, after which U.S. KS incidence declined and survival improved; however, persistent racial and sex disparities remain. Our aim was to characterize 1999-2020 trends in KS incidence and mortality in the United States overall, and by race and sex, and to quantify changes in disparities over time.

Methods: We extracted KS case and death counts from the CDC WONDER database (ICD-10 codes B21.0, C46). Age-adjusted incidence rates (AAIR) and mortality rates (AAMR) per 100,000 were calculated by year, race, and sex. Temporal trends were evaluated using the Mann-Kendall test (Kendall's τ), and between-group differences by t-test (α = 0.05).

Results: From 1999 to 2020, 27,886 KS cases and 4,380 deaths occurred. Overall AAIR was 0.99 in men versus 0.10 in women, and AAMR 0.16 versus 0.01 (both p < 0.001). Black men experienced the highest AAIR (2.23) and AAMR (0.40), significantly exceeding White men (0.79 and 0.13; p < 0.001). Incidence declined in both sexes (men: -46.7%, τ = -0.920; women: -58.9%, τ = -0.848; both p < 0.001). Mortality declined in men (-66.4%, τ = -0.581; p < 0.001). Among women, AAMR levels were very low throughout (mean ≈ 0.01 per 100,000); the end-to-end change from 1999 to 2020 was + 28.6%, yet the Mann-Kendall test did not identify a monotonic trend (τ = - 0.303; p = 0.060), reflecting early declines followed by year-to-year fluctuation around a low baseline.

Conclusion: Although KS incidence and mortality have declined markedly since 1999, Black men remain disproportionately affected. Focused public health efforts and enhanced access to HIV care are essential to close these gaps.

Clinical trial number: Not applicable.

Background: Human papillomaviruses (HPVs) are prevalent sexually transmitted infections and a leading cause of cervical and other anogenital cancers worldwide. This study aimed to determine the prevalence and genotype distribution of HPV in Pap smear samples from women attending gynecology clinics at Dr. Soliman Fakeeh Hospital in Jeddah, Saudi Arabia, between September 2022 and July 2023.

Methods: This cross-sectional study analyzed 260 samples using nested PCR and Sanger sequencing to identify HPV genotypes.

Results: The overall HPV prevalence rate was 6.9%. (18/260, 95% CI: 3.84-10.01%). High-risk HPV (HR-HPV) genotypes 16 (33.3%), 18 (16.7%), and 58 (5.6%) were identified, along with low-risk HPV (LR-HPV) genotype 6 (33.3%). Genotypes 11 and 67 were also detected in 5.6% of cases each. Age-specific analysis revealed the highest prevalence of HPV in the 31-40 age group, at 3.5% (p = 0.04), with HPV16 being significantly more prevalent in this age group. Saudi participants exhibited a higher prevalence rate of 61.1% (11/18) than non-Saudi participants at 38.9% (7/18). Although HPV was more common in non-Saudis, this difference was not statistically significant (p = 0.39). Cytological findings showed that 88.9% of HPV-positive cases had negative cytology, underscoring the need for HPV screening beyond cytological abnormalities.

Conclusions: These findings highlight the importance of continued surveillance, targeted vaccination efforts, and improved screening programs in Saudi Arabia. Increasing awareness of HPV and enhancing vaccination rates, especially among younger age groups, could significantly reduce the burden of HPV-related diseases. Future research should focus on broader epidemiological factors and evaluate the impact of HPV vaccination programs on genotype distribution and prevalence trends.

Hepatitis B virus (HBV) integration and persistent covalently closed circular DNA (cccDNA) are key drivers of hepatocarcinogenesis and remain uncured by current nucleos(t)ide analog (NA) therapy. While high-barrier NAs like entecavir effectively suppress viral replication, they do not eliminate transcriptionally active HBV integrants. In this exploratory study, we analyzed HBV surface (HBs) gene truncation mutations in four patients with HBV-related hepatocellular carcinoma (HCC), including two with prior lamivudine exposure. Next-generation sequencing of DNA and RNA from serum, tumor, and para-neoplastic liver tissues revealed truncation variants, such as sW172* and sW182* were, exclusively in the two lamivudine-experienced patients. These variants were predominantly enriched in tumor RNA, raising the possibility of clonal selection during hepatocarcinogenesis. No truncation mutations were observed in the two patients treated solely with entecavir, despite detectable intrahepatic cccDNA. These findings support the hypothesis that transcriptionally active HBV integrants, possibly shaped by prior lamivudine treatment, may contribute to HCC via truncated HBs protein expression. The selective presence of certain mutants in tumor tissue suggests a potential biological role, though further validation is needed. Given the small sample size and limited number of lamivudine-experienced cases, our observations should be interpreted with caution. Nevertheless, the results highlight the relevance of antiviral treatment history in shaping HBV mutational profiles and raise the possibility that integrant-derived HBs truncation variants could serve as biomarkers for HCC risk stratification. Early detection of such variants may help refine surveillance strategies in virally suppressed patients and inform future therapeutic approaches.

Background: China is among the largest contributors to the global cervical cancer burden. Problems such as insufficient vaccine supply, high vaccine prices, and insufficient policy support hindering vaccine popularization need to be solved.

Methods: In the present study, we employed a qualitative research methodology to retrieve and organize policy documents on cervical cancer from 31 provincial and central governments by the documentation method.

Results: The current relevant action program of the Chinese government places strong emphasis on screening and treatment; however, the absence of a consistent national HPV vaccination policy remains the most critical gap in China's strategy to achieve elimination.

Discussion: Based on the findings of this study, several key recommendations emerge to advance China's political commitment to the Global Strategy to Accelerate the Elimination of Cervical Cancer.