To describe the pathogenesis of human papillomavirus (HPV) and recurrent respiratory papillomatosis (RRP) caused by HPV6/11, immunologic and oncogenic properties, and currently available treatment strategies and to identify and discuss potential treatment targets that can become new foundations for development of future treatments.

A comprehensive literature search was conducted using PubMed and Google Scholar utilizing search terms which includes "recurrent respiratory papillomatosis" "human papillomavirus" "HPV" "laryngeal papillomatosis" in combination with keywords "physiology" "treatment" "surgery" "adjunct therapy" "antiviral therapy" "gene therapy". No particular inclusion/exclusion criteria and no chronologic limitation were set during the search for studies to be used as references.

HPV infection begins with breaches in the epithelial barrier where it gains entry and access to the undifferentiated basal layer keratinocytes where the HPV genome interact with the host cell through the production of viral proteins encoded by the early and late gene regions facilitating viral entry, replication and proliferation. Oncoproteins interfere with host immune surveillance mechanism, promote growth factor signaling, and create a tumor microenvironment resulting in uncontrolled cell proliferation and progression of HPV infection. While high-risk HPV types integrate into the host genome and aggressively promote oncogenesis, low-risk HPV remain superficial with limited oncogenic activity and immune activation which allows avoidance of inflammation induction and cytolysis thereby preventing significant antigen production and facilitates immunosurveillance evasion. The current standard of treatment of RRP is surgical debulking using lasers or cold instruments with or without and adjuvant therapies like antivirals, interferons, VEGF/EGFR inhibitors, and immunomodulators. Novel immunotherapies such as gene therapies and immune checkpoint inhibitors show promising results in boosting immune responses and reducing the frequency of surgical interventions.

The treatment for recurrent respiratory papillomatosis still remains as a challenge due to its high recurrence rates needing repeated surgical and medical intervention attributed to its capability to evade the host immune responses. With the current standard of treatment, advances in the understanding of HPV pathogenesis paved a way for development of new treatment strategies. Understanding the complexities of the cellular and immune mechanisms involved between HPV and the host immune system will provide us with better foundation in identifying potential treatment targets in the future.

We aimed to evaluate awareness of HPV and its associated cancers, attitudes toward HPV vaccination, and vaccination rates in individuals with anogenital warts. This cross-sectional study was conducted at Sakarya University Training and Research Hospital using a questionnaire completed by individuals diagnosed with anogenital warts. A total of 105 respondents were included in the study, comprising 80 males (76.2%) and 25 females (23.8%). The mean age of participants was 34.7 ± 11.2 years. HPV awareness was 70.5%, while cervical cancer awareness was 38.1%. Women demonstrated significantly higher levels of HPV and cervical cancer awareness, as well as knowledge of Pap smear testing, compared to men. Women were also significantly more likely than men to express willingness to vaccinate their children against HPV (84.0% vs. 58.8%, p = 0.039). Higher education levels were associated with increased awareness of HPV, HPV vaccination, and willingness to vaccinate children. Physicians were the primary source of HPV-related information across the cohort. HPV vaccine awareness was 73.3%, but the overall vaccination rate was only 10.5%, with women showing significantly higher vaccination rates than men (24% vs. 6.2%, p = 0.021). The most commonly reported barriers to vaccination were cost (60%) and lack of information (45.7%). None of the participants had vaccinated their children. This study highlights that awareness of HPV and its vaccination is associated with gender and education level but does not translate into higher vaccination rates. Efforts should focus on targeting men and individuals with lower educational attainment by strengthening physicians' roles in public education. Incorporating HPV vaccination into national programs and implementing culturally tailored campaigns may effectively improve vaccination rates.

The relationship between different weight class and mortality risk remained uncertain in cervical cancer patients. Thus, we conducted the study to assess the association between different body weight classes and survival outcomes in patients with cervical cancer.

This was a retrospective cohort study including 6908 cervical cancer patients from the Taiwan Cancer Registry database. A COX regression model was used to evaluate the relationship between different weight classes and time-to-event outcomes of overall survival and cancer-specific survival at three years.

The median follow-up time was 4.64 ± 2.55 years. Our study revealed that the underweight group had a significantly higher risk of overall death [hazard ratio (HR) = 1.65, 95 % confidence interval (CI) = 1.37, 1.99] than the normal-weight group. Overweight patients had a significantly lower risk of overall death (HR = 0.81, 95 % CI = 0.71, 0.93), whereas the obesity group had an insignificant lower risk of overall death (HR = 0.92, 95 % CI = 0.75, 1.13) compared with the reference group.

After controlling for confounding factors, underweight patients with cervical cancer had a higher risk of overall death than normal-weight patients with cervical cancer. Our study indicates that underweight cervical cancer patients had a higher risk of overall death compared with normal-weight cervical cancer patients. Furthermore, the overweight patients had a significantly lower risk of overall death. More strategies are needed to be addressed especially in public health field regarding women's weight class and cancer mortality issues.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with up to 90% of females infected at some point in their lifetime. While most HPV infections will be cleared by the immune system within 2 years, persistent HPV infection may result in anogenital warts, dysplasia of the cervix, vagina, vulva, and squamous cell carcinoma. This chapter will review the epidemiology, microbiology, progression, and treatment of HPV-related genital disease in women.

Felis catus papillomavirus (FcaPV) was first discovered in 2002. Seven genotypes (FcaPV-1/-2/-3/-4/-5/-6/-7) have been reported to date, at least one of which (FcaPV-2) is suggested to be implicated in squamous cell carcinoma (SCC); however, relevant epidemiological data on Japanese cats are limited. There is one report on relatively low FcaPV-2 prevalence in cats with SCC, largely in the Tokyo region. In this study, we investigated the prevalence of each FcaPV genotype in cats with SCC largely drawn from a peripheral region of Japan (Kyushu). Formalin-fixed paraffin-embedded (FFPE) specimens from 107 cats with SCC were subjected to DNA extraction for type-specific PCR assays, followed by confirmatory nucleotide sequencing. Overall, 16 cases (15.0%) were positive for FcaPV, and the results detected for FcaPV-1/-2/-3/-4/-5/-6/-7 were 0/107 (0.0%), 7/107 (6.5%), 4/107 (3.7%), 1/107 (0.9%), 3/107 (2.8%), 1/107 (0.9%), and 1/107 (0.9%), respectively. Our results suggest that FcaPV-2 is the prevalent papillomavirus type in cats with SCC across Japan, but the figure is lower than in other countries. This is also the first report on the detection of FcaPV-6 and FcaPV-7 in Japan, which previously have only been reported in Australia and New Zealand, respectively.

Innate immunity is the immune system that organisms possess from birth. It is primarily responsible for the rapid, nonspecific recognition of pathogens when they invade, activating the host's immune response to eliminate. Cervical cancer is one of the most well-known tumors caused by human papillomavirus (HPV) infection. As the first line of defense against pathogens, innate immunity plays a crucial role in the response to HPV invasion, and there has been significant research in this area in recent years. The findings suggest that innate immune responses not only contribute to the clearance of HPV but may also facilitate the spread of the virus and the carcinogenic transformation of cervical epithelial cells. In this review, we comprehensively examine the activation of innate immune responses during HPV infection, the mechanisms by which HPV evades these immune defenses, and the role of innate immunity in promoting cervical intraepithelial neoplasia. Additionally, we explore the characteristics of innate immune responses within the tumor microenvironment of cervical cancer. Furthermore, we summarize recent advances in understanding the various mechanisms by which innate immune responses can be activated, with a focus on potential therapeutic implications. By reviewing the latest research, this article aims to provide valuable insights and stimulate further investigation into the role of innate immunity in HPV-associated cervical lesions, potentially leading to more effective strategies for prevention and treatment in the future.

While the tumor-suppressive functions of p53 are well established, the role of its homolog, TAp73, in cancer remains incompletely characterized and is a subject of active investigation. In this study, we observed downregulation of TAp73 protein expression in cervical cancer tissues, which significantly correlated with adverse clinical outcomes. Through co-expression network analysis, we identified functional associations between TAp73 and key pathways involved in lipid metabolism and redox homeostasis-both critical regulators of ferroptosis, an iron-dependent form of programmed cell death mediated by lipid peroxidation. Mechanistically, we demonstrate that TAp73 promotes ferroptosis by directly upregulating the transcription of β-transducin repeat-containing protein (β-TRCP), thereby facilitating the ubiquitin-dependent degradation of nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of cellular antioxidant defenses. This TAp73-mediated suppression of NRF2 activity renders cells more susceptible to ferroptotic death. Furthermore, TAp73 expression is transcriptionally induced during ferroptosis through the combined inactivation of enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, and activation of E2F transcription factor 1 (E2F1). Notably, pharmacological inhibition of EZH2 synergized with sulfasalazine (SAS) to enhance ferroptosis in vivo, an effect largely dependent on TAp73. Together, these findings delineate a novel ferroptosis regulatory axis-EZH2/TAp73/β-TRCP/NRF2-and highlight its potential as a therapeutic target for cervical cancer intervention.

High-risk human papillomavirus (hrHPV) genotype is needed for adequate cervical cancer screening and HPV vaccination program evaluation as recommended by different guidelines. We aimed to assess the rate of HPV infection and HPV genotype distribution using vaginal self-sampling in a cohort of unscreened reproductive-age women in Ethiopia. A community-based cohort study was conducted with women aged 23-46 living in Adama, Ethiopia. A total of 885 self-collected vaginal swabs were obtained and tested for hrHPV genotypes with the real-time polymerase chain reaction technique. The overall hrHPV prevalence was 21.1% (187/885, 95% confidence interval [CI]: 18.5-24.0). Among women living with human immunodeficiency virus, 46% (30/56) (95% CI: 33.7-59) were hrHPV positive compared with 19% (157/820) (95% CI: 16.2-22) of human immunodeficiency virus-negative women. The most frequent genotypes were HPV16 (3.1%), HPV51 (3.1%), HPV35 (2.6%), HPV56 (2.6%), HPV52 (2.4%), HPV31 (2.5%), and HPV39 (2.5%). Among the 187 HPV-positive women in self-samples, HPV 16/18 was found in 21% (39), HPV 16/18/45 was found in 24% (44), and HPV 16/18/31/33/45/52/58 was prevalent in 56% (104). Out of 116 biopsies, 7% (8) had cervical intraepithelial lesions and worse identified. Of these eight cervical intraepithelial lesions and worse patients, only 25% tested positive for HPV-16; none tested positive for HPV-18 or 45. One out of five women tested positive for hrHPV genotypes. Other HPV genotypes not covered by the quadrivalent HPV vaccine but associated with clinically significant cervical high-grade lesions or cancer were detected in 75%. It is more effective to prevent cervical cancer by switching to the nine-valent HPV vaccine.

Cervical cancer possesses high morbidity and mortality rates, and a comprehensive understanding of its molecular underpinnings is essential for advancing clinical management strategies. The innate immune sensor STING, which activates type I interferon signaling, plays a pivotal role in enhancing anti-tumor activity. Despite increased attention to STING's involvement in cervical cancer, the regulatory mechanisms governing its protein homeostasis remain poorly understood. In this study, it is found that the BAG2-STUB1 complex regulates ubiquitin proteasomal degradation of STING, which affects the development of cervical cancer. Mechanistically, BAG2 inhibits ubiquitination of STING and stabilizes it by interacting with STING. Specifically, BAG2 inhibits STUB1 from attaching the K48-linked ubiquitin chains at K338 and K370 of STING by forming a complex with STUB1. Functionally, enhanced BAG2 expression suppresses cervical cancer progression by activating the type I interferon pathway in a STING-dependent manner. Notably, clinical cervical cancer samples revealed a positive correlation between BAG2 and STING levels, with low BAG2 expression is strongly linked to advanced disease and poor prognosis in cervical cancer. Collectively, these findings elucidate the molecular mechanism by which the BAG2-STUB1 complex regulates STING homeostasis, underscoring BAG2's potential as a diagnostic biomarker and therapeutic target in cervical cancer.

As more countries introduce the HPV vaccine, it is important to understand the validity of vaccination measures. This is especially true in low- and middle-income countries (LMICs) where public health monitoring of vaccination data may have delays or gaps, so alternative measurement approaches are often necessary. Parental report is a common approach for measuring routine childhood vaccination, but it has not been evaluated for HPV vaccination in LMICs.

We conducted household surveys in Kenya (n = 146) and Malawi (n = 98) with parents/guardians and their daughters who were age-eligible for HPV vaccination. We compared parents'/guardians' reports of HPV vaccination status to daughters' reports; the latter was assumed to be the "gold standard" measure.

88 % of Kenyan parents/guardians and 82 % of Malawian parents/guardians agreed with their daughters' reported HPV vaccination status. It was more common for parents/guardians to under-report (i.e., to say their daughter was unvaccinated but the girl said she had received dose(s)) than the inverse. Agreement with one's daughter was higher among parents/guardians who reported data from vaccination cards versus using recall, and among parents/guardians who expressed more versus less confidence in their knowledge. We did not find many differences in accuracy of report by parent/guardian characteristics, although in Kenya there were small and statistically significant negative associations with parental age, household income, and more girls in the household (the latter was also significantly negatively associated with report accuracy in Malawi).

In countries where surveys will commonly be used to measure HPV vaccination status, we found very high agreement of parents/guardians with their daughters' reported receipt of the vaccine. These results are similar to findings from the literature about routine childhood vaccination measurement. This suggests that researchers, clinicians, and practitioners can use parent/guardian-reported HPV vaccination of their daughter as a relatively good proxy of her own reported immunization status especially in settings without universal use of vaccination cards or registries.

This Opinion summarizes the strategies for anticancer treatment in p53-mutated head and neck squamous cell carcinoma (HNSCC). It examines six strategies for anticancer treatment in p53-mutated HNSCC: 1. direct reactivation of mutated p53; 2. activation of p63; 3. activation of p73; 4. degradation of mutated p53; 5. blocking the p53-regulated oncogenic microRNA; and 6. blocking the p53-regulated oncogenic long non-coding RNA. Since HNSCC has a high p53 mutation rate compared to other types of cancers, these strategies for combating p53-mutated HNSCC may prove useful for generating new ideas or methods for developing treatments for other cancers with p53 mutations. This article also explores other factors that may impact the effectiveness of anticancer therapies in p53-mutated HNSCC.

Haematological malignancies are one of the most common tumors, with a rising incidence noted over recent decades. Viral infections play significant roles in the pathogenesis of these malignancies globally. This review delves into the contributions of various known viruses-specifically Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), human T-cell leukemia virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), human cytomegalovirus (HCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human papillomavirus (HPV)-in the development of haematological malignancies. These viruses are shown to drive tumorigenesis through mechanisms, such as metabolic reprogramming, epigenetic modifications, and remodeling of the immune microenvironment. By directly disrupting fundamental cellular functions and altering metabolic and epigenetic pathways, these viruses foster an immune milieu that supports both viral persistence and tumor growth. A thorough understanding of these viral oncogenic processes is crucial not only for etiological discovery but also for developing targeted interventions. This review emphasizes the need for continued research into the specific ways these viruses manipulate the host cell's metabolic and epigenetic environments, aiming to provide insights that could guide future advancements in treatment modalities.

Liquid biopsy offers a noninvasive method to identify and monitor tumor-derived biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, microRNAs, and tumor-educated platelets, that provide real-time insights into the biological behavior of gynecological cancers. The detection of these markers has the potential to revolutionize cancer management by enabling earlier detection, providing novel data to personalize treatments, and predicting disease recurrence before clinical imaging and predicting disease recurrence before clinical imaging can confirm progression, thereby also guiding complex clinical decision-making. However, because this new "omics" layer introduces additional complexity, it must be fully understood, from its biological rationale to technical development and clinical integration, to prevent confusion or misapplication. That is why, focusing on 14 critical fields of inquiry, our goal is to map the current state of liquid biopsy from bench to bedside while highlighting practical considerations for clinical integration. Each topic integrates recent advances in assay sensitivity, biomarker variability, and data interpretation, underscoring how standardized protocols and robust analytical methods are pivotal for reliable results. We then translate these findings into disease-specific insights, examining how liquid biopsy could refine early detection, minimal residual disease assessment, and therapy guidance in endometrial, cervical, and ovarian cancers. Although several FDA-approved assays and promising commercial tests illustrate the field's rapid evolution, many translational hurdles remain, including the need for harmonized protocols, larger prospective clinical trials, and cost-effectiveness analyses. Crucially, our synthesis clarifies the pivotal role of interdisciplinary collaboration. Oncologists, laboratory scientists, and industry partners must align on standardized procedures and clinically relevant endpoints. Without such coordination, promising biomarkers may remain confined to research settings, limiting their practical benefit. Taken together, our review offers a translational view designed to contextualize liquid biopsy in gynecological oncology.

Background/Objectives: This study evaluates the diagnostic performance of DNA methylation testing, alone and in combination with cervical cytology, for high-grade squamous intraepithelial lesion (HSIL) detection. Methods: A prospective study was conducted on 170 high-risk HPV (hr-HPV)-positive women. DNA methylation (QIAsure®) and cervical cytology were performed prior to cervical large loop excision of the transformation zone (LLETZ). Sensitivity, specificity, and area under the curve (AUC) metrics were calculated, including stratified analyses for HPV16/18 and other hr-HPV genotypes. Results: DNA methylation alone achieved a sensitivity of 69.7%, specificity of 79%, and an AUC of 0.796 for HSIL detection. The combination of cervical cytology and DNA methylation improved sensitivity to 94.7%, specificity to 76.3%, and AUC to 0.860. Stratification by HPV genotype revealed that in HPV16/18-positive cases, DNA methylation alone reached an AUC of 0.790, while the combination with cytology significantly enhanced performance to 0.917. DNA methylation alone demonstrated an AUC of 0.744 for other hr-HPV types, and the combined approach achieved an AUC of 0.849. Specificity for the combined approach was notably higher in HPV16/18-positive women (88.9%) than in other hr-HPV cases (72.4%), whereas the sensitivity of the combined approach was significantly higher in both groups (94.5% vs. 95%, respectively). Conclusions: The integration of DNA methylation with cervical cytology significantly enhances diagnostic accuracy for CIN2+ lesions, especially in HPV16/18-positive cases. However, the comparatively lower AUC and specificity observed in other hrHPV types suggest the need for further optimization to enhance accuracy in non-16/18 infections. These findings support the integration of methylation-based testing with cytology as a valuable triage strategy for improving cervical cancer screening and patient management.

Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.

Human papillomavirus (HPV)-associated cervical cancer risk is greater in people with HIV, although this has been at least partially attenuated by antiretroviral medication, enhanced cervical screening and HPV vaccination. People with perinatally acquired HIV may remain at higher risk due to lifelong immunosuppression and potentially reduced vaccine effectiveness. In this study in people with a cervix with perinatally acquired HIV, we explored cervical high-risk HPV (hrHPV) prevalence and HPV serostatus.

Participants were recruited from a London HIV service between 2020 and 2022. Cervical samples from those sexually active were analysed for hrHPV (Cepheid GeneXpert) and cytology, and, if abnormal, a referral was made to colposcopy. Serum samples were tested for antibodies against HPV6/11/16/18/31/33/45/52/58. A self-reported questionnaire including HPV vaccination history was completed.

Fifty-seven people were recruited with a median age of 25 years (range 18-34). Of those providing a cervical sample, 15/47 (32%) were hrHPV-positive and 12/40 (30%) had abnormal cytology; 1/17 referred for colposcopy had CIN2 (6%); 7/15 (47%) with hrHPV were below the national screening age of 24.5 years (range 19-23), and 9/15 (60%) reported previous HPV vaccination. No vaccinated participants had hrHPV16/18. Of those vaccinated, 37/39 (95%) were seropositive for HPV16 and 30/39 (77%) for HPV18. Two vaccinated participants were seronegative for HPV16/18; both had detectable HIV viral loads and CD4 counts <200 cells/μL at recruitment.

In this small observational study we identified a 32% prevalence of cervical hrHPV. Cervical screening and HPV vaccination remain vital in this group, with further data required to inform screening guidelines for this population.

Human papillomavirus (HPV) infection is a major global health challenge and is closely related to the occurrence of diseases such as cervical cancer. Unfortunately, effective treatments are still lacking. In view of the advantages of antibody drugs, antibody-targeted therapy may become one of the means of treatment and prevention of HPV infection. This study explores the potential of antibody-targeted therapy using immunization with HPV nine-valent vaccine in Leghorn chickens. The resulting egg yolk antibodies (IgY) was extracted from eggs using the bitter-ammonium sulfate method and confirmed through SDS-PAGE analysis. The neutralizing titer was performed by pseudovirus-neutralizing antibody experiments, which could reach 1:2000 (18.2 μg/mL). This successful preparation of IgY against HPV 6/11/16/18/31/33/45/52/58-L1 protein showed its potential as a therapeutic agent, particularly post-HPV16 infection. This work lays the groundwork for HPV-specific IgY preparation and contributes to advancing targeted therapies for cervical cancer, prompting further research in HPV-related therapeutic approaches.

Human papillomaviruses (HPV) cause almost all cervical cancer cases globally, with the high-risk genotypes 16/18 causing at least 70 % of cancers, of which most cases occur in low-to-middle-income countries. Prophylactic vaccination plays a major role in the prevention of cervical cancer, which could effectively prevent the incidence of HPV infection. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralizing antibodies, which form the basis of all currently licensed HPV vaccines. There are six approved prophylactic HPV vaccines. All these vaccines are designed to prevent HPV 16 and 18-associated cervical precancers, thereby preventing approximately 70 % of the cancers. This review looks at the current HPV prophylactic vaccines, their mechanism of action, vaccination schedules, and the cost of different vaccines.

Cervical cancer burden due to recurrent human papillomavirus (HPV) infections necessitates the urgent need to impede viral proliferation targeting the oncogene E6 of the high-risk serotype HPV16. This study aims to identify a small molecule from a natural product library that could prevent a tumorigenic complex of E6 with p53 in HPV16-positive cervical cancer cells. In silico methods such as high-throughput virtual screening (HTVS) of natural product like library ZINC database followed by atomistic molecular dynamics (MD) simulations were performed to identify lead natural compound. This was validated with in vitro analysis using HPV16 positive SiHa cells and CaSki cells by MTT and flow cytometry assays. Virtual screening identified top 10 compounds with high affinity for HPV16 E6. The docking scores, Protein-Ligand Interaction Profiler analysis, MD simulation and molecular mechanics Poisson Boltzmann surface area-based binding energy estimation narrowed down the search to ZINC1797251, a molecule with stable binding, low energy scores and consistent H-bonds, establishing that it could prevent interaction of p53 and E6. ZINC1797251 inhibited the proliferation of SiHa and CaSki cells with a GI50 values of 615.40 and 417.30 nM, respectively. The compound reduced HPV16 E6, while increased p53 positive populations in SiHa and CaSki cells. Treatment with ZINC1797251 induced the G1 cell phase arrest and promoted early and late phase apoptosis in these cells. The restoration of tumor inhibitory activity of p53 in HPV-infected cervical cancer cells to promote apoptosis could be achieved using the ZINC molecule-ZINC1797251. However, further studies are deemed essential for further developments.

One-quarter of US women who are at risk for cervical cancer delay screening. Self-collected (SC) cervical screening was recently US Food and Drug Administration (FDA)-approved in the US for use in a health care setting only; an at-home SC option is crucial to address clinic-related barriers to screening.

To clinically validate the use of an SC device that was designed for optimal at-home performance, safety, ease-of-use, and dry storage and transport.

This nonrandomized clinical trial used a prospective method comparison study design. Participants aged 25 to 65 years were recruited from 16 clinical sites in the US including community and academic practices from November 20, 2023, to April 5, 2024. Data analysis was conducted from April to August 2024.

Eligible participants collected a sample with the SC method, followed by a clinician-collected (CC) sample. The SC sample was eluted into PreservCyt at the laboratory and both samples were tested on an FDA-approved high risk human papillomavirus (hrHPV) test approved for primary screening. Participants were followed up for safety and completed usability and screening preference surveys.

The primary outcome measures were positive percentage agreement (PPA) and negative percentage agreement for detection of hrHPV between the SC and CC samples. Other study measures included clinical sensitivity for high grade cervical dysplasia and usability.

Of 609 screening-eligible participants, 599 (262 aged 30-39 years [43.7%]; 583 identified as female [97.3%]) had paired SC-CC samples, of which 582 had valid paired samples included in the end point analysis. Among the 582 evaluable paired samples, the PPA between SC compared with paired CC samples for detection of hrHPV was 95.2% (95% CI, 92.1%-97.1%; 278 of 292 participants). The absolute clinical sensitivity for detection of high-grade cervical dysplasia was 95.8% (95% CI, 86.0%-98.8%; 46 of 48 participants), equivalent to the CC (relative sensitivity, 1.00). Nearly all participants (555 of 601 participants [92.3%]) reported that the device instructions were easy or very easy to understand and also that they would choose SC if they knew the results were comparable to CC results (560 of 602 participants [93.0%]).

In this nonrandomized clinical trial, SC samples collected with the device showed equivalent clinical sensitivity and exceeded the PPA end point for cervical screening. This SC method was found to be easy to use and to be a preferred option with high clinical performance intended for use in an at-home setting.

ClinicalTrials.gov Identifier: NCT06120205.

Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality.

The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.

Cervical cancer ranks third in mortality and fourth in incidence among women worldwide as one of the leading causes of death from cancer in females. The main reason behind cervical carcinogenesis is long-term infection with high-risk human papillomavirus (HPV) genotypes, particularly HPV16 and HPV18. This review investigates HPV distribution across the world, along with cervical cancer molecular development mechanisms and current treatment strategies. Epidemiological data show that disease patterns vary significantly between different geographic regions because underdeveloped nations bear a higher disease burden. The molecular mechanisms of oncogenes E6 and E7 disrupt tumor suppressor pathways, while epigenetic modifications through DNA methylation and miRNA dysregulation promote malignant cell transformation. The reduction in HPV infection through prophylactic vaccination has shown promise, yet barriers related to accessibility and coverage still exist. The therapeutic technologies of gene expression inhibitors together with immunotherapies and epigenetic targeting agents show promise but require optimization to achieve specific targeting while minimizing off-target effects. A combined approach that integrates HPV vaccination with early diagnosis and molecular-specific therapies represents the most effective method to manage cervical cancer impact. The future care of patients will require increased translational research along with better immunization programs to drive prevention and therapeutic outcomes.

To assess the predictors of Chinese parents of girls' decision stage about the Human Papillomavirus (HPV) vaccination.

Two hundred and seventy-three parents of girls aged 9-17 with no HPV vaccination history were recruited to complete an online survey between September-December 2023. We assessed factors thought to influence decisions about HPV vaccination, including sociodemographics, HPV general knowledge, HPV vaccination knowledge, attitudes, and decisional conflict. Parents were asked to choose the decision stages among Stage 1 (have not thought), Stage 2 (considering), and Stage 3 (decided). Predictors of the decision stage were assessed with univariate and multivariate multinomial logistic regression.

The parents of the three decision stages accounted for 48.4%, 29.7%, and 22.0%, respectively. Parents of older girls were more likely to be in the "considering" stage (OR = 1.29) than the "haven't thought" stage. A higher sense of being uninformed was associated with lower odds of being in the "considering" stage (OR = 0.97). Additionally, greater feelings of uncertainty were linked to lower odds of being in the "decided" stage (OR = 0.95) than the "haven't thought" stage.

This study highlights the importance of understanding the various stages of decision-making in HPV vaccination among Chinese parents. Parents' subjective feelings of being informed and certainty appear to be significant factors in advancing through the decision-making stages. Future research should develop and explore the impact of specific knowledge and valued based tools and decision aids.

Cervical cancer is the most common malignant tumor of the reproductive tract in women and poses a serious threat to their health. Cervical cancer screening is primarily conducted through the detection of HPV or cytological examination. In this study, we analyzed the prevalence, genotyping of HPV, and cervical cytology among women in Shannan city, Tibet, China, between 2021 and 2022, to guide the prevention of cervical cancer among local women. This is the first large-scale cervical cytology screening study conducted in the southern region of the province.

Between January 2021 and December 2022, 15,493 women participated in HPV genotype testing, and 16,775 women underwent ThinPrep cytologic tests. HPV prevalence and genotype distribution were analyzed for the entire population. Furthermore, the samples were stratified by age group and altitude to analyze the HPV infection rate and distribution of cervical cytological abnormalities.

The prevalence of HPV in Shannan city was 7.91%, with HPV16 and HPV18 affecting 1.21%. Single infections (95.92%) were more common than multiple infections (4.08%). The overall HPV infection rate peaked in the cohort < 25 years of age (13.25%). Furthermore, HPV infection rates and cervical cell abnormalities varied according to the administrative division in Shannan city, and this difference was attributed to various altitudes.

Among HPV carriers, the infection rate peaks in women aged 25 years, after which it declined annually, and the probability of coinfection is relatively low. Additionally, we found that high-altitude areas exhibited elevated HPV prevalence but fewer cervical abnormalities, suggesting complex environmental, genetic, and cultural influences on infection and disease progression. Based on these data, effective recommendations can be made for cervical cancer screening and HPV prevention in local communities.

Endometrial cancer (EC) is the fourth-most frequent cancer among the female population and a leading cause of death. Multiple factors are susceptible to causing tumorigenesis, including obesity, lack of physical activity, diabetes mellitus, high concentration of estrogen during menopause, unopposed exposure to estrogen, duration of menses, nulliparity and infertility. Human papillomavirus (HPV) is a double-stranded DNA virus, with certain genotypes exclusively human. HPV plays a major role in some cancers (cervical cancer, head and neck cancer, lung cancer, and anogenital cancers). Given the intricate correlation between HPV and cervical cancer, the scientific community conjectured that HPV may be implicated in the carcinogenesis of the endometrium. In this review, we will direct our interest towards previous studies that focused on the expression of HPV on EC samples and cover how both conditions might connect to each other.

Cervical cancer has the infection by the Human Papillomavirus (HPV) as one of the main conditions for its development. Photodynamic Therapy (PDT) is a non-invasive treatment that combines the interaction between oxygen, light, and a photosensitizing molecule, resulting in cellular damage. HPV - infected cells because they are metabolically more active, can be better affected by this technique, promoting an alternative topic treatment for Cervical Intraepithelial Lesions (CIN). The present prospective and randomized study compared three PDT protocols applied to 31 patients with high-grade CIN and infected by HPV. Protocols used LEDs with a wavelength of 630 nm and a fluence of 150 J/cm2 as a light source, with different number of sessions and intervals between the three groups. There was no statistical difference between the protocols, however, we noticed a clinical difference that indicates a better response to PDT in the treatment with two PDT sessions, and an interval of 21 days between sessions. In this protocol, after 120 days of therapy, 50 % of patients had a regression in the lesion, presenting cytology compatible with CIN I or chronic cervicitis and after 6 months there was an 80 % cure rate. Furthermore, 50 % of patients who, before treatment, were carriers of high-risk HPV had a complete viral load clearance. Therefore, we conclude that a greater number of sessions, as well as a longer interval between the treatments day, is an efficient method to enhance the results of PDT, allowing more time for regeneration and viral clearance of the cervical tissue.

Uterine cancer is a leading gynecological malignancy with increasing incidence and mortality rates, particularly in regions such as the United States and China. Despite advancements in treatment, current therapeutic strategies are often limited by tumor heterogeneity, therapy resistance, and a lack of targeted treatment options. These challenges underscore the urgent need for novel therapeutic approaches to improve patient outcomes. This study aims to investigate the role of miR-126-5p in uterine cancer pathogenesis, focusing on its potential as a therapeutic target to address these limitations.

The study employed HeLa (cervical cancer) and Ishikawa (endometrial adenocarcinoma) cell lines to evaluate the effects of miR-126-5p on cell proliferation, migration, and apoptosis. The molecular mechanisms underlying these effects were further explored by examining the involvement of the RICTOR/AKT signaling pathway.

miR-126-5p was demonstrated to significantly inhibit cell proliferation and migration while promoting apoptosis in both HeLa and Ishikawa cell lines. These effects were mediated through the RICTOR/AKT signaling pathway, with no involvement of the RICTOR/PCK pathway.

The findings reveal miR-126-5p as a critical regulator of uterine cancer progression and a promising therapeutic target. By addressing the limitations of current therapies, this study provides a foundation for the development of miRNA-based treatments, offering new hope for improving outcomes in uterine cancer patients.

Canonical Wnt signaling plays a key role in tumor cell proliferation which correlates with the accumulation of β-catenin resulting inactivation of the network of targets such as GSK3β, Axin, CK1. Uncontrolled expression of β-catenin leads to different types of cancers and other diseases such as sarcoma and mesenchymal tumor formation. However, β-catenin is an attractive target for cervical cancer. In the present study, the compounds such as Doxorubicin and Zinc conjugated with Doxorubicin were screened against β-catenin using Molecular Docking, Molecular Dynamics Simulation, MM/GBSA, and DFT approaches to explore their insights. The study further demonstrated that the binding energy of Zn conjugated with Doxorubicin has shown -7.2 kcal/mol and Doxorubicin registers -5.9 kcal/mol against β-catenin. The disruption between the β-catenin/Tcf-4 complex was observed through the Zinc-Doxorubicin complex, both the proteins are separated about 12 Å. The Zn-Doxorubicin was stabilized with the hydrophobic residues such as Val349 of β-catenin and Phe21 of Tcf-4. The DFT analysis using the B3LYP/6-31g(d,p) method explores that Zn-doxorubicin in complex with the binding site residues has shown the HOMO-LUMO gap of 2.55 eV. The binding free energy calculations exhibit the Zn conjugated Doxorubicin favors in the study by showing ~ 3 kcal/mol difference with Doxorubicin. The Zn-conjugated Doxorubicin will be discussed in the context of cervical cancer with the hope of improving drug efficacy and reducing toxicities for the betterment of the patient's quality of life.

Maternally expressed gene 3 (MEG3), a long non-coding RNA, plays a pivotal role in various biological processes, including tumorigenesis. Aberrant expression of MEG3 has been implicated in several cancers, including genitourinary malignancies. This comprehensive review explores the multifaceted functions of MEG3 in the context of genitourinary cancers through unravelling the molecular mechanisms underlying the influence of MEG3 on cellular proliferation, apoptosis, invasion, and metastasis. Additionally, we discuss the potential clinical implications of MEG3 as a biomarker and therapeutic target in genitourinary cancers. By unraveling the intricate role of MEG3 in these biological processes, this review aims to contribute to the development of novel strategies for the diagnosis and treatment of genitourinary malignancies.

Viral-human protein interactions are critical for viral replication and modulation of the host immune response. Structural modeling of these interactions is vital for developing effective antiviral therapies and vaccines. However, 99% of experimentally determined binary host-viral interactions currently lack structural information. We aimed to address this gap by leveraging computational protein structure prediction methods. Using extensive benchmarking, we found AlphaFold to be the most accurate structure prediction model for host-pathogen protein interactions. We then predicted the structures of 11,666 binary protein interactions across 33 viral families and created the most comprehensive atomic-scale 3D viral-host protein interactomes till date ( https://3d-viralhuman.yulab.org ). By integrating these interactomes with genetic variation data, we identified population-specific signatures of selection on variants coding for interfaces of viral-human interactions. We also found that viral interaction interfaces were less conserved than non-interface regions, a striking trend that is opposite to what is observed for host interfaces, suggesting different evolutionary pressures. Systematic analyses of interface sharing between host and viral proteins binding to the same host protein revealed mutation rate-dependent differences in interface mimicry. Similar mutation rate-dependent differences were seen in the interface sharing between viral proteins binding to a host protein. We also found that the patterns of E6 protein binding to KPNA2 differed between high- and low-risk oncogenic human papillomaviruses (HPVs), and clustering based on these binding patterns allowed the classification of HPVs with unknown oncogenic risk. Our interface mimicry analyses also unveiled a novel mechanism by which herpes simplex virus-1 UL37 suppresses the antiviral immune response through disruption of the TRAF6-MAVS signalosome interaction. Overall, our comprehensive 3D viral interactomes provide a resource at unprecedented scale and resolution that will enable researchers to explore how variation and signatures of selection influence viral interactions and disease progression. This tool also facilitates the identification of conserved and unique interaction patterns across viruses, empowering researchers to generate testable hypotheses and ultimately accelerate the discovery of novel therapeutic targets and intervention strategies.

Aging is a key risk factor for many diseases, including cancer, and a better understanding of its underlying molecular mechanisms may help to prevent, delay, or treat age-related pathologies. Epigenetic alterations such as DNA methylation (DNAme) changes are a hallmark of aging and form the basis of so-called epigenetic clocks, yet their functional relevance and directionality in different organs during disease development is often unclear.

Here, we link cell-specific age-related DNAme changes with three key hallmarks of aging and cancer (senescence, promoter methylation in genes associated with stem cell fate, and dysregulated proliferation) to comprehensively dissect their association with current and future cancer development, carcinogen exposure or preventive measures, and mortality using data in different organs from over 12,510 human and 105 mouse samples, benchmarking against existing epigenetic clocks.

Our findings offer insights into the association of functionally enriched groups of age-related DNAme changes with cancer, identify sites perturbed earliest during carcinogenesis, as well as those distinct between cancer and reprogramming that could inform strategies to prevent teratoma formation upon in vivo reprogramming. Surprisingly, both mouse and human data reveal accelerated aging in breast cancer tissue but decelerated epigenetic aging in some non-cancer surrogate samples from breast cancer patients, in particular cervical samples.

This work provides evidence for discordant systemic tissue aging in breast cancer.

ObjectiveThis study aims to explore HPV genotyping in the cervical specimen using VirCapSeq by comparing the results with the reverse blot hybridization assay (REBA).MethodsA secondary cross-sectional data of HPV genotypes in 35 cervical specimens was obtained from VirCapSeq and REBA methods. The .FASTQ files were downloaded from the NCBI Sequence Read Archive (SRA) (accession number PRJNA766412) and HPV genotyping was bioinformatically analyzed by mapping the sequences to the PaVE database. HPV genotypes detected by REBA and NGS were compared. All specimens were stratified by histology into cervical intraepithelial neoplasia grades 1 (CIN1) and 2/3 (CIN2/3).ResultsNGS via VirCapSeq detected HPV DNA in 100% of the samples, whereas the REBA (hybridization-based) assay diagnosed HPV DNA in 85.71%. While the limitation of the conventional methods for HPV genotyping is the use of primers or probes, NGS detected a broader range. The results showed that mixed infections were detected in all samples by NGS, with HPV16 and HPV52 being the most abundant genotypes.ConclusionsHPV genome abundance, coverage, and diversity were associated with detection discrepancies between the methods, highlighting the enhanced sensitivity and diagnostic capabilities of NGS. These findings underscore the potential of NGS technologies for comprehensive HPV genotyping, advancing cervical cancer screening, and epidemiological studies. Future research should address cost barriers and expand cohort sizes to validate these findings.

The vitamin D endocrine system, primarily mediated by its main metabolite calcitriol and the vitamin D receptor (VDR), plays a critical role in numerous human physiological processes, ranging from calcium metabolism to the prevention of various tumors, including cervical cancer. In this study, we comprehensively investigated the genomic regulatory effects of calcitriol in a cervical cancer model. We examined the transcriptional changes induced by calcitriol in CaSki cells, a cervical cell line harboring multiple copies of HPV16, the primary causal agent of cervical cancer. Our microarray findings, revealed that calcitriol regulated over 1000 protein-coding genes, exhibiting a predominantly repressive effect on the CaSki cell transcriptome by suppressing twice as many genes as it induced. Calcitriol decreased EPHA2 and RARA expression while inducing KLK6 and CYP4F3 expression in CaSki cells, as validated by qPCR and Western blot. Functional analysis demonstrated that calcitriol effectively inhibited key processes involved in cancer progression, including cell proliferation and migration. This was further supported by the significant downregulation of MMP7 and MMP13 mRNA levels. Our microarray results also showed that, in addition to its effects on protein-coding genes, calcitriol significantly regulates non-coding RNAs, altering the expression of approximately 400 non-coding RNAs, including 111 microRNA precursors and 29 mature microRNAs, of which 17 were upregulated and 12 downregulated. Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.

Human papillomavirus (HPV) genotyping is essential for cervical cancer screening and prevention. The AllplexTM HPV28 real-time PCR kit, using different chemistry and results analysis compared with its predecessor, the AnyplexTM II HPV28 kit, has recently been launched. This study aims to compare the AllplexTM HPV28 and AnyplexTM II HPV28 assays in detecting and genotyping the 13 high-risk (HR)-HPV types.

Between 2022 and 2023, 459 cervical samples from women undergoing cervical cancer screening were selected. These samples were analysed by liquid-based cytology and tested by both kits concurrently.

AllplexTM HPV28 Ct values correlated well with AnyplexTM II HPV28 signal intensity scores. No significant differences between assays were observed in overall and genotype-specific HR-HPV prevalence determined in all samples and according to cytological results. In addition, no significant differences were identified between assays in the detection of single and multiple HR-HPV infections. Most of the discordant results corresponded to samples showing weak HR-HPV signals and multiple HR-HPV types.

Our results demonstrate that the AllplexTM HPV28 kit can be used for HPV genotyping, with results overall similar to those obtained with the AnyplexTM II HPV28 kit and the addition of Ct values for patient follow-up. The clinical implications of the potentially reduced sensitivity of the AllplexTM HPV28 kit in detecting HPV31 (p =  0.07) and HPV39 (p =  0.08) warrant further investigation in subsequent studies.

High-risk HPV infection is a necessary but not sufficient factor for the development of precancerous lesions and cervical cancer. Beyond mere HPV positivity, the persistence of infection over time plays a crucial role. This study aims to evaluate the clearance and persistence rates of HPV 16 and 18 genotypes.

The cervical cytology results were reported using the 2014 Bethesda System classification. The cervical cytology samples were analyzed using the Roche Cobas® 4800 HPV tests. Patients with any HPV genotype other than 16 or 18, those with missing data, those who were lost to follow-up, those who underwent excisional procedures or hysterectomy, and those with high-grade cervical dysplasia were excluded from this study.

Among 191 patients (mean age: 41.2 ± 0.6 years, 16.8% postmenopausal), the mean follow-up was 21.6 ± 0.7 months. No significant differences were found between the clearance and persistence groups in age, follow-up duration, cervical biopsy, or endocervical curettage results. However, HPV 16 had a higher persistence rate (28.2%), and abnormal cytology was more frequent in the persistence group (p = 0.038).

Around 25% of patients had persistent HPV infection. Close monitoring is essential for those with CIN 1 on initial colposcopy, as they may have a higher risk of progressing to high-grade dysplasia compared to those without dysplasia.

The role of human Papillomavirus (HPV) in metabolic reprogramming is implicated in the development and progression of cervical cancer. During carcinogenesis, cancer cells modify various metabolic pathways to generate energy and sustain their growth and development. Cervical cancer, one of the most prevalent malignancies affecting women globally, involves metabolic alterations such as increased glycolysis, elevated lactate production, and lipid accumulation. The oncoproteins, primarily E6 and E7, which are encoded by high-risk HPVs, facilitate the accumulation of several cancer markers, promoting not only the growth and development of cancer but also metastasis, immune evasion, and therapy resistance. HPV oncoproteins interact with cellular MYC (c-MYC), retinoblastoma protein (pRB), p53, and hypoxia-inducible factor 1α (HIF-1α), leading to the induction of metabolic reprogramming and favour the Warburg effect. Metabolic reprogramming enables HPV to persist for an extended period and accelerates the progression of cervical cancer. This review summarizes the role of HPV oncoproteins in metabolic reprogramming and their contributions to the development and progression of cervical cancer. Additionally, this review provides insights into how metabolic reprogramming opens avenues for novel therapeutic strategies, including the discovery of new and repurposed drugs that could be applied to treat cervical cancer.

Cervical cancer, closely linked to Human Papillomavirus (HPV) infection, remains a significant health threat for women worldwide. Conventional HPV detection methods, such as reverse transcription polymerase chain reaction (RT-PCR), rely on nucleic acid amplification (NAA), which can be costly and time-consuming. This study introduces an NAA-free electrochemical Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based biosensor designed to detect HPV 16 and HPV 18 L1 genes simultaneously. The system utilizes a Cas9-single guided RNA complex to initiate a selective cleavage reaction, releasing Methylene blue or Ferrocene-labeled fragments correlate to L1 gene concentrations. These fragments then interact with modified gold electrodes immobilized with a complementary probe, allowing precise electrochemical signal measurement during hybridization. The biosensor offers a wide detection range from 1 fM to 10 nM, with detection limits as low as 0.4 fM for HPV 16 L1 and 0.51 fM for HPV 18 L1, providing a sensitive and efficient solution for L1 gene detection. Additionally, its specificity and sensitivity closely match RT-PCR results in clinical testing, highlighting its potential for molecular diagnostics and point-of-care applications.