Search Results (3,143)

Head and neck squamous cell carcinoma (HNSCC) is biologically and clinically dichotomous according to HPV status, a distinction that fundamentally dictates the design, implementation, and interpretation of liquid biopsy strategies. Conventional anatomical imaging lacks sufficient sensitivity for minimal residual disease (MRD) detection, contributing significantly to treatment failure and suboptimal clinical outcomes. This review provides a critical, evidence-based synthesis of the three principal circulating analytes, circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), and their evolving roles in real-time, non-invasive molecular monitoring. Critically, the clinical readiness of these analytes differs substantially: while ctDNA, particularly HPV-related ctDNA, is approaching clinical validation for MRD detection and recurrence surveillance in HPV-positive HNSCC, exosomes and CTCs remain investigational tools hindered by ongoing technical challenges including lack of standardized assays, limited reproducibility across platforms, and insufficient prospective validation. We review how the presence of a clonal, virally derived DNA target in HPV-positive HNSCC contrasts with the heterogeneous somatic mutational landscape of HPV-negative tumors, necessitating divergent analytical platforms and yielding distinct clinical utility profiles for MRD detection and recurrence surveillance. We further outline a pragmatic translational pathway focused on assay standardization, particularly for exosomes and CTCs where this foundational work is most urgently needed, integration of complementary multimodal liquid biopsy approaches, and rigorously designed prospective interventional clinical trials to establish clinical utility. Collectively, these efforts aim to transition HNSCC management from reactive, anatomy-based surveillance to proactive, molecularly guided precision oncology, with the potential to improve therapeutic decision-making and patient outcomes. Full article

Anal human papillomavirus (HPV) and cancer prevalence are increasing. Therefore, this study investigated the prevalence of anal HPV and associated risk factors, as well as HPV genotype-specific concordance at cervical and anal sites and associated risk factors among women of Eastern Cape Province, South Africa. A total of 326 women aged 18–60 were recruited from an Eastern Cape community health facility. HPV DNA was detected in cervical and anal specimens using the Seegene Anyplex™ and Allplex™ II HPV28 assay (Seegene Inc., Seoul, Republic of Korea), respectively. Anal HPV was detected in 68.1% (95% CI: 62.9–72.9) and independent predictors were cervical HPV positivity (AOR: 2.40, 95% CI: 1.39–4.14, p = 0.002), abnormal cytology (AOR: 3.12, 95% CI: 1.29–7.55, p = 0.012), single marital status (AOR: 3.55, 95% CI: 1.24–10.17, p = 0.018), and having more than three lifetime sexual partners (AOR: 1.75, 95% CI: 1.03–2.98, p = 0.039). Anal high risk (HR)-HPV types were detected in 50.9%, with HPV-58 (13.2%), HPV-68 (11.0%) and HPV-52 (9.2%) being the most dominant types. HPV genotype-specific cervical and anal concordance was observed in 33.5% of cases, with HPV-58 (7.1%), HPV-68 (4.9%), and HPV-35 (4.6%) being the most dominant. Women who were positive for cervical HPV infection (AOR: 3.24, 95% CI: 2.36–4.45, p < 0.001), anal HPV infection (AOR: 2.70, 95% CI: 2.01–3.63, p < 0.001) and abnormal cervical cytology (AOR: 2.01, 95% CI: 1.36–2.96, p < 0.001) had substantially higher odds of anal–cervical HPV concordance compared to those who were negative. High anal HPV prevalence and HPV genotype-specific anal and cervical concordance were observed among Eastern Cape women. Understanding anal HPV, HPV genotype-specific anal–cervical concordance, and associated factors can contribute to strategies towards anal HPV and associated disease prevention. These findings warrant further longitudinal investigation in future studies. Full article

Background: Persistent infection with high-risk human papillomavirus (hr-HPV) is the necessary agent of cervical cancer, yet its molecular definition remains heterogeneous. Multiple molecular approaches have been developed to characterize HPV persistence, including repeated detection of viral DNA, assessment of viral oncogene expression, and analysis of HPV-related DNA methylation. These approaches originate from different scientific traditions and reflect distinct conceptualizations of persistence. Objective: To synthesize and compare molecular methods used to detect persistent HPV infection through a narrative review and to clarify how different biomarkers conceptualize HPV persistence and disease progression. Methods: We conducted a narrative review in accordance with the RAMESES guidelines. Medline, Scopus, and the Cochrane Library were searched for original studies published between 2016 and 2025 investigating molecular markers of HPV persistence. An interpretive synthesis was performed to identify research traditions, underlying assumptions, and clinical implications. Results: Three major molecular narratives were identified. Persistent DNA positivity defines persistence as repeated detection of the same HR-HPV genotype over time and reflects an epidemiological–virological perspective with high sensitivity but limited specificity. Persistent oncogene expression, assessed by E6/E7 mRNA detection, conceptualizes persistence as active viral oncogenic activity and shows improved specificity for clinically relevant lesions. Persistent epigenetic imprint, measured by DNA methylation of viral and host genes, captures cumulative biological effects of long-term infection and is strongly associated with high-grade lesions and cervical cancer. These narratives represent complementary stages along a continuum of molecular persistence. Conclusions: Molecular markers of HPV persistence reflect the evolving understanding of cervical carcinogenesis, progressing from repeated viral DNA detection to oncogenic activity and stable epigenetic alterations. These complementary biomarkers represent different biological stages of persistent infection and may improve risk stratification in HPV-based screening and triage strategies. Full article

Background: Cervical cancer remains a major global health burden, with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) representing the two predominant histological subtypes. Comparative clinicopathological patterns between SCC and ADC in contemporary cohorts remain of interest, but inference is often limited by small single-center datasets. Methods: We conducted a retrospective single-center cohort analysis of cervical cancer patients treated between 2020 and 2024. Demographic, clinical, and pathological variables, including p16 immunohistochemistry, histological subtype, differentiation grade, FIGO stage, and survival status, were analyzed. Comparative analyses were performed using appropriate exact tests, and survival was assessed using Kaplan–Meier methods. Results: The cohort included 85 patients: 69 with squamous cell carcinoma and 16 with adenocarcinoma. Both subtypes demonstrated similarly high p16 positive rates (89.9% vs. 93.8%, p = 1.00). Menopausal status emerged as a distinguishing factor (p = 0.0047), with SCC patients more likely to be postmenopausal. SCC patients were older on average (52.16 vs. 48.2 years: p = 0.0131). Analyses involving p16 status were interpreted descriptively due to the very small number of p16-negative cases. Kaplan–Meier analysis revealed significant survival differences by clinical stage (log-rank p = 0.03), with high-stage patients showing progressive decline from 95% to 73% survival over five years, while low-stage patients maintained 100% survival. Conclusions: In this retrospective single-center cohort, SCC and ADC showed similar p16 positivity rates and clinical stage remained the most informative prognostic variable. Apparent subtype-related demographic differences and multivariable associations should be considered hypothesis-generating rather than definitive. Larger multicenter studies with standardized pathology and p16 assessment, direct HPV testing/genotyping, and more complete clinical and prevention-related data are needed before prognostic or clinical conclusions are drawn. Full article

Background/Objectives: HPV vaccination is highly effective in preventing HPV-related cancers when administered before viral exposure. However, vaccination practices for patients already diagnosed with gynaecological cancers remain poorly characterized. Understanding clinicians’ perspectives and barriers is essential for optimizing preventive strategies in oncologic care. Methods: We conducted an international, web-based survey among members of the European Society of Gynaecological Oncology (ESGO) and the European Network of Young Gynaecological Oncologists (ENYGO). The questionnaire explored clinicians’ attitudes, practices, and perceived obstacles regarding HPV vaccination in patients with gynaecological cancer or pre-invasive disease across multiple clinical scenarios and age groups. Results: A total of 149 respondents from 33 countries completed the survey. Most clinicians supported HPV vaccination for patients treated for cervical precancer (78–82% for patients under 45 years), and even for invasive cervical cancer (57–62%). Recommendations varied by patients’ age, cancer type, and treatment status. For endometrial and ovarian cancer, endorsement ranged from 16% to 53%, depending on patient age. Timing of vaccination was a point of divergence: some clinicians favoured vaccination immediately after treatment for CIN2+, while others recommended delaying vaccination depending on HPV test results. Reported barriers discouraging HPV vaccination recommendations included misinformation (69.8%), lack of patient education materials (52.3%), and time constraints (48.3%), alongside economic factors and uncertainty about efficacy in oncologic settings. Conclusions: The survey shows that HPV vaccination is often recommended beyond evidence-supported indications. Randomized trials have not demonstrated a reduction in CIN2+ recurrence with adjuvant vaccination, and no evidence supports vaccination in women with invasive gynaecological cancers. These findings reveal a gap between clinical practice and available evidence, highlighting the need for clearer, evidence-based guidance. Full article

Human papillomavirus (HPV), especially high-risk HPV types, is a significant public health concern due to its association with various cancers and increased risk of acquiring other sexually transmitted infections (STIs). In most cases, host immunity rapidly responds to and clears HPV infections, but persistent or latent infections can increase susceptibility to cancer. A better understanding of how HPV interacts with and evades the immune response is vital to understanding disease progression and guiding the next generation of vaccines and immunotherapies. This review article provides a comprehensive overview of the immune mechanisms involved in HPV infection, highlighting the roles of T cells and other immune subsets. We discuss the immune evasion strategies employed by HPV and subsequent modulation of the immune microenvironment. Additionally, we explore the current therapeutic landscape and emerging immunotherapeutic approaches under investigation. By unveiling the intricacies of the immune response to HPV, we may inform improved strategies for the treatment of HPV-related diseases. Full article

Background: Cervical carcinoma remains a widespread cancer worldwide, primarily caused by persistent infection with high-risk human papillomavirus (HPV). HPV types 16 and 18 account for approximately 70% of cervical cancer cases. Although prophylactic HPV vaccines are commercially available, their high cost and reliance on expensive expression platforms limit their accessibility in developing countries. Objectives: This study aimed to develop a cost-effective, plant-based HPV vaccine candidate by expressing capsomeric HPV-16 and HPV-18 L1 antigens in Brassica oleracea (broccoli). Methods: Modified L1 from HPV types 16 and 18 were designed to retain capsomeric assembly and fused with heat-labile enterotoxin B subunit (LTB). Immunoinformatics analyses were used to assess antigenicity, epitope distribution, and structural characteristics. Codon-optimized genes were cloned using Gateway^® technology and expressed in broccoli via Agrobacterium-mediated transformation. Transgenic plants were validated by PCR and qRT-PCR. Protein accumulation was quantified, and immunogenicity was evaluated in mice. Results: PCR and qRT-PCR confirmed the stable integration of two copies of the LTB-L1 transgenes in broccoli plants. Western blotting detected L1 protein at ~56.5 kDa, indicating the cleavage of the LTB-L1 fusion protein. The correct folding of L1 capsomeres was verified by antigen-capture ELISA. The recombinant proteins accumulated to approximately 0.33% and 0.35% of total soluble protein for HPV-16 and HPV-18, respectively. The immunization of mice with transgenic L1 induced significant humoral immune responses, comparable to those elicited by purified VLPs. Conclusions: The results demonstrate broccoli as a promising platform for the expression of immunogenic HPV L1 capsomeres and highlight its potential for the development of affordable, plant-based HPV vaccines. Full article

Background: Low-grade squamous intraepithelial lesions (LSIL/CIN1) are among the most common abnormalities detected in cervical cancer screening, particularly in the era of primary HPV testing. Despite their low oncogenic potential, persistence of LSIL is still frequently interpreted as a marker of progression risk, often leading to intensified surveillance or excisional treatment and raising concerns about overtreatment. Methods: We conducted a retrospective cohort study including women with persistent LSIL managed through active surveillance in a real-world clinical setting. Time-to-event analyses were performed using Kaplan–Meier estimates to evaluate CIN3-free survival. The association between HPV16 status and progression to CIN3 was assessed using Cox proportional hazards models. The proportional hazards assumption was tested using Schoenfeld residuals, and a prespecified landmark analysis at 24 months was performed to explore potential time-dependent effects. Results: A total of 82 women were included, with a median follow-up of 48 months (range 24–78). Progression to histologically confirmed CIN3 occurred in 7 cases (8.5%). Most CIN3 events (6/7, 85.7%) were diagnosed within the first 24 months of surveillance, followed by a plateau in long-term CIN3-free survival. HPV16-positive women showed a higher incidence of CIN3 compared with non-HPV16 women. In Cox regression analysis, HPV16 positivity showed a higher estimated hazard of CIN3; however, the association did not reach statistical significance and confidence intervals were wide, reflecting the limited number of outcome events. Conclusions: In women with persistent LSIL/managed by active surveillance, progression to CIN3 was uncommon and predominantly occurred early during follow-up. Long-term persistence of LSIL alone did not confer a sustained excess risk of high-grade disease. These findings support a risk-based management approach and suggest that excisional treatment based solely on LSIL persistence may contribute to overtreatment without meaningful oncologic benefit. However, given the limited number of events, the results should be interpreted cautiously and primarily as descriptive evidence. Full article

Objectives: To assess the impact of organized (OgS) versus opportunistic screening (OpS) on grade, extent, and surgical management of cervical lesions, and to evaluate human papillomavirus (HPV)-based versus cytology-based screening within OgS. Methods: This retrospective study analyzed 9830 women undergoing conization (1992–2021). Data included screening modality, histology, cervical intraepithelial neoplasia grade 3 (CIN3) linear extension, and cone volume. Statistical analysis employed chi-square test, Student’s t-tests, Cochran–Armitage test for trend, and Firth’s penalized multivariate logistic regression to identify independent predictors of invasive disease. Results: Of 9830 patients, 5097 (52%) were referred from OgS and 4733 (48%) from OpS. OgS patients were significantly older (40.0 vs. 37.0 years; p < 0.001). In the final decade, OgS achieved a significantly lower rate of invasive carcinomas compared to OpS (1.1% vs. 2.7%; p < 0.001). Mean CIN3 extension and cone volume were significantly lower in OgS (6.5 mm; 1150 mm³) than in OpS (7.1 mm; 1580 mm³; p < 0.001). Within OgS, HPV-detected CIN3 lesions were smaller than cytology-detected ones (5.9 vs. 6.4 mm; p < 0.001). Long-term analysis showed a borderline downward trend in invasive cancer for OgS (p = 0.089), whereas OpS remained stable at higher risk levels. Multivariate analysis confirmed the screening model as an independent predictor of invasiveness: OpS was associated with a two-fold increased risk of invasive cancer compared to OgS (adjusted odds ratio: 1.99; 95% confidence interval: 1.41–2.83; p < 0.001). Conclusions: OgS identifies high-grade precancers earlier and with smaller excisional requirements. OpS is associated with significantly higher invasive cancer rates and larger conizations. Multivariate data reinforce OgS as a superior framework, effectively halving the risk of invasive disease compared to OpS. Full article

The cooking and eating quality (CEQ) of rice is primarily regulated by the Wx and SSIIa genes. Multiple allelic variations in these genes exist in rice, but the effect of allelic combination of Wx and SSIIa on rice CEQ was less understood. In this study, the Wx and SSIIa genes of 164 rice accessions were sequenced, and the effects of nucleotide variation, both individually and in combination, on physicochemical properties such as apparent amylose content (AAC), gelatinization temperature (GT), pasting viscosities and gel texture were analyzed. Six Wx alleles were identified, with the highest AAC found in the Wx^lv allele and the lowest in the wx allele. No significant difference in AAC for the same genotype harvested from two locations, Hangzhou and Sanya, was observed. Three SSIIa alleles were identified, i.e., G/GC, G/TT, and A/GC. The genotype with the G/GC exhibited significantly higher GT than those with G/TT and A/GC genotypes. However, the GT of the same genotype was higher in Hangzhou than in Sanya, suggesting an environmental effect. Under the same Wx^lv allele background, the gel hardness (HD) of G/TT allele of SSIIa was the highest among all combinations, and significantly higher than that of G/GC. Under the same wx allele background, the peak viscosity (PV), hot paste viscosity (HPV), and cold paste viscosity (CPV) of G/GC were significantly higher than that of G/TT and A/GC. Under the same G/GC allele of SSIIa background, Wx^lv had a slightly lower peak temperature (Tp) and a slightly higher enthalpy of gelatinization (ΔHg) than other allele combinations. Under the same G/TT allele of SSIIa background, Wx^b had a significantly lower onset temperature (To), Tp and conclusion temperature (Tc) than other combinations. This study indicated that variation in the Wx gene primarily affects AAC, viscosity and gel texture, with its interaction with SSIIa influencing GT, while variation in the SSIIa gene primarily affects GT, with its interaction with Wx influencing pasting viscosity. Full article

Background: The approach to adenocarcinoma in situ (AIS) is challenged by diagnostic complexity, limited high-quality evidence, and heterogeneous guidance. Methods: We conducted a narrative comparative review of global guidelines/recommendations (2012–2025; search updated 1 October 2025), extracting data across 38 topics related to AIS management and classifying indications into five categories of coverage/consensus. Results: Twenty documents from national or supranational bodies were included. A cross-guideline consensus emerged on eight core items (colposcopy for any glandular cytologic abnormality; role of HPV test; mandatory histologic confirmation; excisional treatment for histologic AIS; re-excision when margins are involved; criteria and type of hysterectomy; and expert/centralized management). Operational variability emerged in the excisional technique, pathways for discordant results, management during pregnancy, and follow-up protocols. Divergent guidance was most evident for indications to endocervical sampling, criteria for conservative management, and the need for hysterectomy after completed childbearing. Limited-coverage consensus involved the technique of initial histologic sampling, endometrial assessment, and pathways for cytology subtypes. Several areas remained unaddressed. Conclusions: While the essential management of AIS is well defined, uncertainty increases when treatment must be personalized. A core outcome set and rigorous multicenter studies are needed to reduce heterogeneity and enable truly evidence-based personalization. Full article

Vehicular emissions are a significant anthropogenic source of air pollutants in South Africa, driven by urbanisation and industrialisation. Thulamela Municipality in Limpopo Province faces increasing air quality challenges associated with rising vehicle kilometres travelled (VKT) and population growth. A reliable baseline emission inventory is therefore required to inform effective air quality management. This study quantified emissions and developed a vehicular emission inventory (VEI) for Thulamela Municipality using a bottom-up approach for the period 2012–2021. VKT was estimated using odometer readings obtained through a questionnaire-based seven-day vehicle survey, together with registered vehicle population data from the National Traffic Information System (NaTIS). Results indicate that VKT increased over the study period, with light-duty vehicles (LDVs) contributing the most, followed by passenger cars (PCs), heavy-duty vehicles (HDVs), and heavy-passenger vehicles (HPVs). Cumulative emissions of CO, NO_x, PM₁₀, PM_2.5, and SO₂ over the 10 years were 32,781.1, 22,326.0, 1367.8, 1291.7, and 547.2 tons, respectively, with growth rates ranging from 39% to 41%. In 2021, total vehicular emissions reached 6647.6 tons, dominated by CO (56%) and NO_x (38%), with PM₁₀ (3%), PM_2.5 (2%), and SO₂ (1%). LDVs contributed 82% of total emissions, followed by PCs (9%), HDVs (6%), and HPVs (3%). A positive correlation between vehicle numbers and Gross Domestic Product (GDP) further suggests that economic growth is associated with higher emissions. These findings show that vehicular emissions are a key contributor to air pollution in the area and highlight the need for targeted mitigation strategies to improve air quality and protect public health. Full article

Cervical cancer has a high incidence and mortality, and is one of the leading causes of cancer-related deaths among women worldwide. The infection with high-risk subtypes of the human papillomavirus (HPV) represents a crucial factor in the development of precancerous lesions. HPV oncoproteins target multiple host factors to promote uncontrolled cellular proliferation, genomic instability, profound metabolic reprogramming, resistance to apoptosis and immune evasion. Thus, cervical carcinogenesis involves metabolic reprogramming in patient cells, such as enhanced aerobic glycolysis, and altered glutamine, lipid and mitochondrial metabolism, which collectively support the bioenergetic and biosynthetic demands of cancer cells. Cancer cells also activate several mechanisms to adapt and survive under hypoxic/anoxic conditions. The mechanisms underlying cervical carcinogenesis often involve non-coding RNAs. This review aims at summarizing the mechanisms and factors involved in the development and progression of cervical cancer following HPV infection, and offers an overview of the available therapies that have been developed for this disease. Full article

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and malignant transformation in IPs. We retrospectively analyzed 73 patients with histologically confirmed IPs that were treated at three tertiary ENT centers, including radiologic data, HPV DNA detection and p16 immunohistochemistry. Univariate analysis was used to identify factors associated with recurrence and malignant transformation, and restricted exploratory multivariable logistic regression models were used to assess recurrence while minimizing overfitting. Fourteen recurrences (19%) were associated with longer symptom duration (p = 0.003), smoking (p = 0.03), advanced Krouse stage (III–IV) (p < 0.001), frontal sinus origin (p = 0.02), HPV+ DNA (50% vs. 22%, p = 0.048), and p16 loss/reduced expression (p = 0.006). Nine recurrences transformed into carcinoma (12%) and were associated with smoking (p = 0.01). HPV+ was not associated with malignancy (p = 1.00). Recurrence was associated with the advanced stage of the IP, tobacco use, longer symptom duration, frontal sinus origin, HPV+, and p16 loss/reduced expression. Full article