Novel strategies in HPV­16­related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy.

BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.

Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Roles of epidural block in combination with general anesthesia in stress response and immune function of patients after surgery for cervical cancer.

We aimed to explore the roles of epidural block in combination with general anesthesia in the stress response and immune function of patients after surgery for cervical cancer. A total of 108 patients undergoing radical surgery of cervical cancer were randomly assigned into a general anesthesia combined with epidural block (observation) group and a general anesthesia (control) group. Peripheral blood was collected before anesthesia (t0), during anesthesia maintenance, as well as 10 min, 1 d, 2 d and 7 d after surgery. The levels of cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4) and transforming growth factor-ß1 (TGF-ß1) were detected by ELISA, and IFN-γ/IL-4 ratio was calculated. Compared with the control group, the observation group had significantly lower levels of GH, PRL and Cor, proportions of Th2 and Treg cells, and levels of IL-4 and TGF-ß1 during anesthesia maintenance and at each time point after surgery (P < 0.05), but higher proportion of Th1 cells, Th1/Th2 cell ratio, IFN-γ level and IFN-γ/IL-4 ratio (P < 0.05). General anesthesia in combination with epidural block can work better in mitigating the stress response and protecting the immune function of patients after cervical cancer surgery.

Analysis of vaginal flora diversity and study on the role of Porphyromonas asaccharolytica in promoting IL-1ß in regulating cervical cancer.

Cervical cancer, a prevalent malignancy in the female reproductive tract, exhibits a high incidence. Existing evidence indicates a robust correlation between alterations in vaginal flora composition and the progression of cervical cancer. Nevertheless, there is a lack of clarity concerning the specific microorganisms within the vaginal microbiota that are linked to the onset and development of cervical cancer, as well as the mechanisms through which they exert carcinogenic effects. The 16 S ribosomal (rRNA) and metagenomic sequencing technology were used to analyze vaginal microorganisms, and screening for human papillomavirus (HPV) positive cervical cancer-associated microbial markers using fold change in mean bacterial abundance. Moreover, vaginal microenvironmental factors were detected, and the local vaginal inflammatory state in patients with cervical cancer was subjected to assay via qRT-PCR and ELISA. The hub inflammatory genes were screened by transcriptome sequencing after co-culture of bacteria and normal cervical epithelial cells, and an in vitro model was utilized to assess the impacts of inflammatory factors on cervical cancer. Both cervical cancer patients and HPV-positive patients showed significant changes in the composition of the vaginal flora, characterised by a decrease in the abundance of Lactobacillus and an increase in the abundance of a variety of anaerobic bacteria; The microbial sequencing identified Porphyromonas, Porphyromonas_asaccharolytica, and Porphyromonas_uenonis as microbial markers for HPV-associated cervical cancer. Vaginal inflammatory factors in patients with cervical cancer were overexpressed. After Porphyromonas_asaccharolytica intervention on cervical epithelial H8 cells, interleukin (IL)-1ß, a hub differential gene, markedly promoted tumor-associated biological behaviors at the in vitro cytological level in cervical cancer. This study for the first demonstrated that Porphyromonas, Porphyromonas_asaccharolytica, and Porphyromonas_uenonis could serve as novel microbial markers for cervical cancer. Moreover, Porphyromonas_asaccharolytica was identified as having the ability to induce the overexpression of inflammatory genes in cervical epithelial cells to create a favorable microenvironment for the onset and development of cervical cancer. The effects of dysbacteriosis on cervical cancer were microbiologically elucidated.

Altered microbial diversity and composition of multiple mucosal organs in cervical cancer patients.

OBJECTIVES: The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients. METHODS: We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases. RESULTS: Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (pOral_Sob < 0.001, pOral_Shannon = 0.049, pOral_Simpson = 0.013 pFecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota (pVaginal_Pielou = 0.028, pVaginal_Simpson = 0.006). There were also significant differences in the ß-diversity of the microbiota at each site between cases and controls (pOral = 0.002, pFecal = 0.037, pUrine = 0.001, pVaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (pUrine = 0.036) and lymph node metastasis (pUrine_Sob = 0.027, pUrine_Pielou = 0.028, pUrine_Simpson = 0.021, pUrine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors. CONCLUSIONS: Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.

Factors associated with cervical cancer screening among women of reproductive age in Ghana.

BACKGROUND: Cervical cancer remains a leading cause of cancer-related deaths among women in Ghana and other Sub-Sahara African (SSA) countries. Despite the importance of early diagnosis for timely treatment and death prevention, cervical cancer screening among women in developing countries remain very low. Nonetheless, there is a paucity of research examining the factors associated with screening uptake among women of reproductive age in Ghana. Thus, this study fills the scholarly void and contributes to the existing literature by examining the determinants of cervical cancer screening in Ghana. METHODS: Utilizing data from the 2022 Ghana Demographic and Health Survey (GDHS) (N = 15,014 women), and by employing logistic regression models for a cross-sectional analysis, this study evaluated the factors associated with cervical cancer screening in Ghana. RESULTS: Women with tertiary educational attainment (OR = 4.140; 95%CI: 2.960 5.789; p < 0.001), from the richer (OR = 1.968; p < 0.001) and richest households (OR = 2.492; p < 0.001), the married/living with partner (OR = 1.773; 95%CI:1.372 2.290; p < 0.001), the widowed/divorced/separated (OR = 1.888; 95%CI:1.320 2.701; p < 0.001), owners of valid health insurance card (OR = 1.356; 95%CI:1.086 1.693; p < 0.01), visitation to health facility in the past 12 months (OR = 1.312; 95%CI: 1.082 1.590; p < 0.001), those who watched television at least once in a week (OR = 1.395; 95%CI: 1.055 1.846; p < 0.001), as well as those who listened to radio at least once in a week (OR = 1.509; 95%CI: 1.228 1.853; p < 0.001), were all significantly more associated with cervical cancer screening in the study context. Also, ethnicity, religion, and the region of residence significantly predicted cervical cancer screening in the study context. CONCLUSION: Cervical cancer screening in Ghana can be improved by addressing socioeconomic and geographical disparities in the country's healthcare system. To ensure early detection, timely treatment or care and prevention of cervical cancer-related deaths in the country, there must be coordinated efforts by the government of Ghana to improve healthcare access and surveillance systems for cervical cancer cases, particularly, in geographically disadvantage areas.

CD133+/ABCC5+ cervical cancer cells exhibit cancer stem cell properties.

Objective: This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer. Methods: Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers. Results: The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P < 0.01). Notably, proportions of CD44+, CD24+CD44+, ABCC5+, CD24+CD44+ABCC5+, CD44+ABCC5+, CD24+CD44+FOXM1+, CD44+FOXM1+, CD133+ABCC5+, and CD133+FOXM1+ were significantly higher (P < 0.05). Furthermore, the size and number of spheres formed byCD133+ABCC5+ cells were greater in the sorted Hela/Taxol line (P < 0.01), with increased expression of the stem cell marker Sox2 (P < 0.001). Conclusion: The Hela/Taxol cells demonstrate increased tumoral stemness, suggesting that CD133+ABCC5+ may serve as a novel marker for cervical cancer stem cells.

A quantitative analysis of artificial intelligence research in cervical cancer: a bibliometric approach utilizing CiteSpace and VOSviewer.

Background: Cervical cancer, a severe threat to women's health, is experiencing a global increase in incidence, notably among younger demographics. With artificial intelligence (AI) making strides, its integration into medical research is expanding, particularly in cervical cancer studies. This bibliometric study aims to evaluate AI's role, highlighting research trends and potential future directions in the field. Methods: This study systematically retrieved literature from the Web of Science Core Collection (WoSCC), employing VOSviewer and CiteSpace for analysis. This included examining collaborations and keyword co-occurrences, with a focus on the relationship between citing and cited journals and authors. A burst ranking analysis identified research hotspots based on citation frequency. Results: The study analyzed 927 articles from 2008 to 2024 by 5,299 authors across 81 regions. China, the U.S., and India were the top contributors, with key institutions like the Chinese Academy of Sciences and the NIH leading in publications. Schiffman, Mark, featured among the top authors, while Jemal, A, was the most cited. 'Diagnostics' and 'IEEE Access' stood out for publication volume and citation impact, respectively. Keywords such as 'cervical cancer,' 'deep learning,' 'classification,' and 'machine learning' were dominant. The most cited article was by Berner, ES; et al., published in 2008. Conclusions: AI's application in cervical cancer research is expanding, with a growing scholarly community. The study suggests that AI, especially deep learning and machine learning, will remain a key research area, focusing on improving diagnostics and treatment. There is a need for increased international collaboration to maximize AI's potential in advancing cervical cancer research and patient care.

Stereotactic body radiotherapy boost as an alternative to brachytherapy for cervical cancer: a scoping review.

PURPOSE: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer. MATERIAL AND METHODS: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety. RESULTS: Sixteen studies were included, encompassing prospective (n=4) and retrospective cohort studies (n=8), as well as phase I and II trials (n=4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 - 40Gy/3 to 5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86% to 100%, 78% to 92%, and 81% to 92%, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49% to 95%, 50% to 77%, and 50% to 69%, respectively. Two studies reported a pathological complete response rate of 93% and 94% three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14%) and gastrointestinal (0-26%) toxicities. The overall incidence of rectovaginal fistulas ranged from 0-13%. CONCLUSION: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness.

Association of HOTAIR rs7958904 Polymorphism with Cervical Cancer Risk.

Cervical cancer (CC) has been the prominent cause of cancer-associated fatalities among women in developing countries. In terms of occurrence and mortality, it is ranked second in Bangladesh. Although different genetic polymorphisms linked with this cancer have been investigated over time, the association between the HOTAIR rs7958904 variant and cervical cancer is being reported for the first time in Bangladeshi women. RT-PCR-based TaqMan assay was employed to perform this case-control study on 200 cervical cancer patients and 148 healthy volunteers. Both cases and controls had average ages of 57.5 and 52.5 years, respectively. According to Hardy-Weinberg equilibrium, the rs7958904 allele of HOTAIR gene pretended no deviation for both cases and control groups. The genotyping results showed that rs7958904 has a significant correlation to the development of cervical cancer in different genetic association models, such as co-dominant 1 (CC vs. GG: OR = 1.67, p = 0.0435), co-dominant 2 (CC vs. GG: OR = 3.13, p = 0.0006), co-dominant 3 (CC vs. CG: OR = 1.88, p = 0.0384), dominant (CG + CC vs. GG: OR = 1.98, p = 0.004), recessive (CC vs. GG + CG: OR = 2.25, p = 0.005), and allele model (C vs. G: OR = 1.70, p = 0.0006). In conclusion, the HOTAIR rs7958904 variant has a substantial role in cervical cancer development in Bangladeshi women. Further functional studies with a larger population size are required to support our findings.

RBPMS-AS1 sponges miR-19a-3p to restrain cervical cancer cells via enhancing PLCL1-mediated pyroptosis.

Cervical cancer (CC) poses a threat to human health. Enhancing pyroptosis can prevent the proliferation and epithelial-mesenchymal transition (EMT) of tumor cells. This study aims to reveal the candidates that modulate pyroptosis in CC. Accordingly, the common microRNAs (miRNAs/miRs) that were sponged by RBPMS antisense RNA 1 (RBPMS-AS1) and could target Phospholipase C-Like 1 (PLCL1) were intersected. The expression of PBPMS-AS1/miR-19a-3p (candidate miRNA)/PLCL1 was predicted in cervical squamous cell carcinoma (CESC), by which the expression location of RBPMS-AS1 and the binding between RBPMS-AS1/PLCL1 and miR-19a-3p were analyzed. The targeting relationship between RBPMS-AS1/PLCL1 and miR-19a-3p was confirmed by dual-luciferase reporter assay. After the transfection, cell counting kit-8 assay, colony formation assay, quantitative reverse transcription PCR, and Western blot were implemented for cell viability and proliferation analysis as well as gene and protein expression quantification analysis. Based on the results, RBPMS-AS1 and PLCL1 were lowly expressed, yet miR-19a-3p was highly expressed in CESC. RBPMS-AS1 overexpression diminished the proliferation and expressions of N-cadherin, vimentin, and miR-19a-3p, yet enhanced those of E-cadherin, PLCL1, and pyroptosis-relevant proteins (inteleukin-1ß, caspase-1, and gasdermin D N-terminal). However, the above RBPMS-AS1 overexpression-induced effects were counteracted in the presence of miR-19a-3p. There also existed a targeting relationship and negative interplay between PLCL1 and miR-19a-3p. In short, RBPMS-AS1 sponges miR-19a-3p and represses the growth and EMT of CC cells via enhancing PLCL1-mediated pyroptosis.

Urdamycin V from Streptomyces sp induces p53 independent apoptosis in cervical cancer cells inconsiderate of HPV status and inhibited growth of gram-positive human pathogens.

In cervical cancer, loss of p53 or mutant non-functional p53 and hyperactivated mTOR/Akt pathway positively correlates to cancer progression. Urdamycin V isolated from Streptomyces OA293 is a recently isolated novel angucycline derivative that in the present study showcased induction of p53 independent apoptosis in both HPV (Human papillomavirus) positive and negative cervical cancer cell lines. Apoptosis induction was via phosphorylation modulation in the cell growth regulating proteins along mTORC2/Akt/p38/Erk pathway. The compound was also tested against human pathogens and selectively inhibited gram-positive strains, Streptococcus pyogenes and Staphylococcus aureus. The present study put forward urdamycins as a potential therapeutic that places promise for further research.

Evaluation of a Radioiodinated G-quadruplex Binder in Cervical Cancer Models.

We herein describe the radiosynthesis of a 125I-labeled acridine orange derivative ([125I]-C8), acting as a G-quadruplex binder, and its biological evaluation in cervical cancer models, aiming to enlighten its potential as a radioligand for Auger Electron Radiopharmaceutical Therapy (AE-RPT) of cancer. [125I]-C8 was synthesized with a moderate radiochemical yield (ca. 60 %) by a [125I]iodo-destannylation reaction. Its evaluation in cervical cancer HeLa cells demonstrated that the radiocompound has a significant cellular internalization with a notorious accumulation in the cell nucleus. In line with these results, [125I]-C8 strongly compromised the viability of HeLa cells in a dose-dependent manner, inducing non-repairable DNA lesions that are most probably due to the AEs emitted by 125I in close proximity to  the DNA. Biodistribution studies in a murine HeLa xenograft model showed that [125I]-C8 has fast blood clearance and high in vivo stability but poor tumor uptake, after systemic administration. The respective supramolecular conjugate with the AS1411 aptamer ([125I]-C8/AS1411) led to a slower blood clearance in the same animal tumor model, although without improving the tumor uptake. To take advantage of the radiotoxicity of [125I]-C8 against cervical cancer cells other strategies need to be studied, based namely on alternative nanodelivery carriers and/or intratumoral injection approaches.

Clinically validated HPV assays offer comparable long-term safety in primary cervical cancer screening: A 9-year follow-up of a population-based screening cohort.

Molecular testing for human papillomaviruses (HPV) is gradually replacing cytology in cervical cancer screening. In this longitudinal population-based cohort study, 4140 women 20 to 64 years old attending organized screening were tested at baseline by five different screening methods and followed for 9 years. To assess long-term safety, the cumulative risks of CIN2+/CIN3+ were estimated after a negative baseline result obtained by conventional cytology and four clinically validated HPV assays: Hybrid Capture 2 (hc2), RealTime High Risk HPV assay (RealTime), cobas 4800 HPV Test (cobas_4800), and Alinity m HR HPV (Alinity). HPV-negative women at baseline had a substantially lower risk for CIN2+ compared to those with normal baseline cytology: 0.84% (95% CI, 0.46-1.22), 0.90% (95% CI, 0.51-1.29), 0.78% (95% CI, 0.42-1.15), and 0.75% (95% CI, 0.39-1.11) for hc2, RealTime, cobas_4800, and Alinity, respectively, compared to 2.46% (95% CI, 1.88-3.03) for cytology. No differences were observed between HPV assays in longitudinal sensitivity (range: 86.21%-90.36%) and negative predictive values (range: 99.54%-99.70%) for CIN2+ in women ≥30 years, but were significantly different from cytology (p < .05). The 9-year cumulative risk of CIN2+ differed significantly between HPV genotypes, reaching 32.1% (95% CI, 14.5-46.1) for HPV16, 24.9% (95% CI, 4.7-40.8) for HPV18/45, 27.2% (95% CI, 14.6-37.8) for HPV31/33/35/52/58, and 8.1% (95% CI, 0.0-16.7) for HPV39/51/56/59. Four clinically validated HPV assays showed comparable safety and better assurance against precancerous lesions than cytology, but some important differences were identified in the performance characteristics of HPV assays impacting the referral rate. Information about the HPV genotype is valuable for guiding further clinical action in HPV-based screening programs.

Cervical cancer microbiome analysis: comparing HPV 16 and 18 with other HPV types.

Differences in the cervicovaginal microbiome may influence the persistence of HPV and therefore, the progression to cervical cancer. We aimed to analyze and compare the metatranscriptome of cervical cancers positive for HPV 16 and 18 with those positive for other HPV types to understand the microbiome's influence on oncogenicity. RNA sequencing data from a total of 222 invasive cervical cancer cases (HPV16/18 positive (n=42) and HPV "Other types" (n=180)) were subjected to taxonomy classification (Kraken 2) including bacteria, virus and fungi to the level of species. With a median depth of 288,080.5 reads per sample, up to 107 species (38 bacterial, 16 viral and 53 fungal) were identified. Diversity analyses revealed no significant differences in viral or fungal species between HPV16/18 and other HPV types. Bacterial alpha diversity was significantly higher in the "Other HPV types" group for the Observed index (p=0.0074) (but not for Shannon). Cumulative species curves revealed greater species diversity in the "Other HPV types" group compared to "HPV16/18 but no significant differences in species abundance were found between HPV groups. The study did not detect strong significant microbiome differences between HPV 16/18 and other HPV types in cervical cancers. Further research is necessary to explore potential factors influencing the oncogenicity of different HPV types and their interaction with the cervical microbiome.

Quality of Life Post Cervical Cancer Treatment: A Comparison Between Radical Surgery Approach and Radiotherapy and Chemotherapy.

INTRODUCTION: The assessment of quality of life (QoL) in women with cervical cancer is crucial due to the profound changes they undergo during and after treatment. Often, the significance of sexual factors is underestimated, likely due to societal taboos surrounding such discussions. OBJECTIVE: This study aimed to determine the long-term QoL outcomes, particularly focusing on sexuality, among three therapeutic approaches for cervical cancer: chemotherapy, radiotherapy, and brachytherapy; isolated hysterectomy; and hysterectomy combined with radiotherapy. METHODS: Conducted from November 2022 to July 2023, this cross-sectional study involved 131 cervical cancer patients. Their QoL was assessed using the MDASI, FACIT-Cx, and risk factor questionnaires. Results were compared across the three treatment groups, revealing notable differences. RESULTS: Patients undergoing chemo/radio/brachytherapy showed significantly lower QoL scores compared to those undergoing isolated hysterectomy. This was evident in reduced scores across FACIT-Cx subscales for physical well-being, specific concerns, and FACIT-total (p < 0.05). The MDASI results similarly indicated greater symptoms and interference in daily activities for the chemo/radio/brachytherapy group. CONCLUSION: In conclusion, isolated hysterectomy, demonstrated superior QoL outcomes compared to chemo/radio/brachytherapy. Furthermore, the study underscored the importance of addressing sexual concerns in QoL assessments of cervical cancer survivors, emphasizing the need for comprehensive care to enhance overall well-being posttreatment.

A comprehensive review on the role of PIWI-interacting RNA (piRNA) in gynecological cancers.

Gynecological cancers are currently a major public health concern due to increase in incidence and mortality globally. PIWI-interacting RNA (piRNA) are small non-coding RNA consisting of 24-32 nucleotides that plays regulatory role by interacting with piwi family of protein. Recent studies have revealed that piRNAs are expressed in various kinds of human tissues and influences key signalling pathways at transcriptional and post transcriptional levels. Studies have also that suggested piRNA and PIWI proteins display frequently altered expression in several cancers. Recent research has indicated that abnormal expression of piRNA may play a significant role in development and progression of gynecological cancers. Clinical studies suggested that, abnormally expressed piRNAs may serve as diagnostic and prognostic marker, and as potential therapeutic targets in these cancers. In the present review article, we discussed the emerging role of piRNA and their utility as diagnostic and prognostic marker in gynecological cancers.

The Roles of Autophagy-related miRNAs in Gynecologic Tumors: A Review of Current Knowledge for Possible Targeted Therapy.

Gynecological cancers are the leading cause of malignancy-related death and disability in the world. These cancers are diagnosed at end stages, and unfortunately, the standard therapeutic strategies available for the treatment of affected women [including chemotherapy, radiotherapy and surgery] are not safe and effective enough. Moreover, the unwanted side-effects lowering the patients' life quality is another problem for these therapies. Therefore, researchers should search for better alternative/complementary treatments. The involvement of autophagy in the pathogenesis of various cancers has been demonstrated. Recently, a novel crosstalk between microRNAs, small non-coding RNAs with important regulatory functions, and autophagy machinery has been highlighted. In this review, we indicate the importance of this interaction for targeted therapy in the treatment of cancers including gynecological cancers, with a focus on underlying mechanisms.

Subtle Presentation of Two Rare Gynecological Cancers in a Single Patient: A Case Report.

Yolk sac tumors (YSTs) are rare germ-cell malignancies that usually develop in the gonads. Similarly, gastric-type adenocarcinoma of the endocervix (GAS) is a rare kind of gynecological cancer that has piqued interest due to its distinctive clinical and pathological features. These two malignancies in a single patient present a unique and challenging scenario. Here, we present the case of a 33-year-old female who presented with postcoital bleeding and was diagnosed with atypical glandular proliferation consistent with GAS. Interestingly, this patient had a history of a YST treated with left salpingo-oophorectomy and chemoradiation in the Philippines five years prior. A follow-up ultrasound report in the Philippines five months after treatment showed no evidence of residual disease. This case report aims to understand the predisposing factors of these neoplasms and asks if there is a link between them, which is necessary for tailoring surveillance, appropriate therapeutic approaches, and improving patient outcomes.

Accelerating HPV vaccination in Africa for health equity.

Cervical cancer is a preventable disease that continues to burden socioeconomically underserved regions, especially in Africa. Vaccination of adolescents who have never had sex with prophylactic human papillomavirus (HPV) vaccines proves effective in preventing the disease. However, vaccine accessibility and availability are two persistent challenges in low-resource settings. For this commentary, a trend analysis is conducted for national HPV vaccination and coverage rates in Africa, a region with high burden of the disease. This is in consideration of the World Health Organization (WHO) strategy to vaccinate 90% of adolescent girls by the age of 15, as part of strategy to eliminate cervical cancer by 2030. The analysis estimated that the rate of incorporating HPV vaccination in national immunization programs in Africa occurs slowly, at a mean wait time of 12 years with estimated coverage rate of 52%. A policy change that harnesses strategic approaches, such as a regionalized vaccination program, is recommended to hasten HPV vaccination for the rest of African countries without a national program.