The evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China.Clinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays.P < 0.001).The overall HPV infection rate was 18.81% (95% CI 18.31–19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24–12.06%), 4.19% (95% CI 3.94–4.44%) and 2.96% (95% CI 2.74–3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15–24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups (This study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.The online version contains supplementary material available at 10.1186/s12985-022-01879-y. Human papillomavirus (HPV) is one of most commonly encountered sexually transmitted infection, which mainly causes cervical cancer and other cancers  . More thCurrently, three licensed HPV vaccines are available, including bivalent (HPV-16 and -18), quadrivalent  and nonavalent vaccines  in mainland China. They were launched and approved for use by China Food and Drug Administration (CFDA) in 2016, 2017 and 2018, respectively , 10. ForShanghai have 16 districts with over 20 million population in its area. Previous studies have investigated the prevalence and genotype distribution of HPV in Zhoupu , MinghanFrom Janauary 2015 to December 2019, women who attended at the Shanghai Putuo Hospital and Liqun Hospital and received HPV DNA genotyping test were included in this restrospective and cross-sectional study. Inclusion criteria for individual were as follows: (1) was ≥ 15 years old; (2) was living in Shanghai city; (3) was first time to receive the test and did not have any treatment; (4) not pregnant and had sexual activity. Finally, a total of 23,866 women with results of genotype-specific HPV were enrolled in this study. This study was approved by the ethics committees of Putuo Hospital, Shanghai University of Traditional Chinese Medicine (PTEC-A-2020-24-1), and the written informed consent was obtained from all the participants at each clinic visit.Cervicovaginal cell samples were collected from each participant by professional gynecologists using plastic brushes . The brushes were placed into sterile tubes containing 3 ml of cell preservation solution  and stored at 4 °C, and finally trasported to our clinical lab within one week for HPV DNA genotype testing.HPV DNA extraction was performed using a domestic commercial available viral DNA extraction kit  according to manufacturers, procedure. HPV detection and genotyping were conducted using Tellgenplex™ HPV DNA Test . The Test is a suspension bead array method that involves PCR, hybridization onto a bead using amplified PCR products and digital singnal processing . In brieBeides overall HPV, type-specific, defined HR, LR and mixed HPV prevalence, we also analyzed the prevalence of several different groupings of HPV genotypes including: (1) categories based on licensed vaccine-preventable HPV genotypes: bivalent (2v) (HPV-16/18), quadrivalent (4v) (HPV-6/11/16/18), nonavalent (9v) (HPV-6/11/16/18/31/33/45/52/58) and non-vaccine HR-HPV (HPV-26/35/39/51/53/56/59/66/68/82); (2) categories grouped according infection feature: single and multiple types infection. (3) responsive classification implicated in oncogenic degree (HPV-16/18/31/33/35/39/45/51/52/56/58/59/68). In addition, The participants were divided into six groups by age , and the prevalence of HPV infection in those age groups was calculated. Moreover, the potential impact of current vaccines in different age groups was also evaluated.P value < 0.05 was considered statistically significant for all analyses.Excel (version 2010), SPSS software (version 22.0) were used for data processing and analysis. Bubble plots were created with ggplot2 and reshape2 packges, and heatmap plot was conducted with pheatmap package in R (version 4.1.2). The 95% confidence interval (CI) for HPV prevalence was estimated. Considering the impact of 4v and 9v vaccines, McNemar exact test and multiple chi-square test were used to compare the significant difference between two paired percentages and prevalence among different groups, respectively. The prevalence of 17 HR-HPV infection was summarized according geographical division of China based on epidemiological studies published from Janauary 2015 to August 2021. Difference in 17 HR-HPV genotypes distribution were visualized by Non-metric Multi-Dimensional Scaling (NMDS) using PAST software [P < 0.001). A similar results was also observed for LR-HPV infection . A downward trend of the HPV prevalence was observed based on year . Single and multiple HPV infection accounted for 13.46% (95% CI 13.03–13.89%) and 5.35% (95% CI 5.06–5.63%) of all the participants. In the multiple infection, double HPV genotypes infection was the most common feature (3.62%). The prevalence rates for HR-HPV, LR-HPV and mix-risk HPV were 11.65% (95% CI 11.24–12.06%), 4.19% (95% CI 3.94–4.44%) and 2.96% (95% CI 2.74–3.17%), respectively. Among all of the HR-HPV women, single HR-HPV positive rate was 9.67%, which was significantly higher than that of multiple HR-HPV infection , HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). In addition, three most commonly detected LR-HPV genotypes were HPV-61 (1.52%), HPV-6 (1.29%) and HPV-81 (1.19%). We found significant differences for most genotypes from 2015 to 2019, except for HPV-26, HPV-42, HPV-44, HPV-61, HPV-81 and HPV-83 , and a significantly higher coverage in 9v vaccine than in 4v vaccine for each age group   and Guan1%  and GMany studies have shown that HPV infection were significantly age-specific –34. In tKnowledge of the genotype distribution of HPV in specific areas will enable the improvement of optimal protective strategies. Previous studies have indicated that HPV-52, -16 and -58 were the most common HPV genotype in many regional of China , 39, 40.This study provides a comprehensive analysis about the characteristics of HPV infection in Shanghai women. There are several limitations of this study. Firstly, this study was a only hospital-based survey including women who visited our hospital and received HPV DNA genotyping from Janauary 2015 to December 2019, which may not represent the general population in Shanghai. Secondly, there is no data of cervical lesion classification due to the inability to obtain complete cytological data of enrolled women. Thirdly, lack information of socieconomic status and sexual behaviors make it difficult to provide practical guidance in prevention of HPV infection.Our data disclosed a very high prevalence of HPV infection in younger women, suggesting the great necessary of HPV screening and vaccination among younger women. High frequency of non-vaccine-coverd HR-HPV genotypes demands a local epidemiological data-based new HPV vaccine in the future.Additional file 1. Prevalence of cervicovaginal human papillomaviruses  stratified by age and geographical areas.


Human papillomavirus (HPV) causes more than one-fourth of infection related cancers globally. The present study summarises the epidemiology of HPV related cancers in India, with a special focus on cervical and oropharyngeal cancer, utilising the National Cancer Registry Programme (NCRP) data. The data on HPV related cancer incidence and treatment were extracted from 28 population-based and 96 hospital-based cancer registries under the NCRP network. Incidence was presented as rates, clinical extent of disease and treatment provided as percentages. Joinpoint regression analysis was performed to calculate annual percent change in age adjusted incidence rates (AARs) over time. Incidence of HPV related cancers for 2025 was projected. Among all cancers, 7.5% were HPV related cancers. Cervical cancer (87.6%) and oropharyngeal cancer (63.2%) were the most common HPV related cancers in India among females and males, respectively. Cervical cancer was highest in Papumpare district  and oropharyngeal cancer among males in East Khasi Hills district Population Based Cancer Registry . In most PBCRS, cervical cancer incidence rate decreased significantly over the period of time. The majority of these cancers presented at locoregional spread stage of the disease and were treated with chemoradiation. The projected incidence of HPV related cancers is expected to increase to 121,302 by 2025. Implementation of effective prevention and control strategies like HPV vaccination and scaling up of screening could reduce the burden of HPV related cancers. Evidence from NCRP serves as the baseline to monitor the impact of HPV related policies and programmes in improving the outcome and prognosis. Globally in 2018, human papillomavirus (HPV) accounted for 31% cancer cases amongst 13% of all human infection related incident cancer cases . In 2018India contributed to 7% of the global cancer incidence and 24% of global HPV related cancer incidence in 2020 . Four ouBased on the monograph findings from the International Agency for Research on Cancer (IARC) and the International Classification of Diseases, Tenth Revision, HPV related cancers are defined as the cancers of cervix uteri C53), vulva (C51), vagina (C52), penis (C60), anus (C21) and oropharynx (C09-C10), oral cavity (C01-C06) and larynx (C32) [, vulva  - National Centre for Disease Informatics and Research (NCDIR) at Bengaluru, India. PBCRs actively collect cancer incidence and mortality data on cancer patients residing for minimum of 1 year prior to diagnosis in the defined geographical area, whereas HBCRs collate information on clinical diagnosis, treatment modalities and outcome from the cancer patients availing treatment and care from various departments in the hospital from any part of the country. The cancer data collected by the NCRP network undergoes rigorous quality checks as per IARC norms. The present analysis utilised the finalised data on HPV related cancer sites reported from 28 PBCRs between 2012 and 2016 and 96 HBCRs between 2012 and 2019 , 11.Five-year age specific population size by sex for the years 2012–2016 was estimated using the 2001 and 2011 India Census data , 14. TheThere were 415,194  incident cancer cases for all sites reported from 28 PBCRs between 2012 and 2016 in India and, 7.5%  were from all the HPV related sites. HBCR data of 2012–2019 reported 64,043 HPV related cancer cases .For all the HPV related cancers, East Khasi Hills district, Meghalaya reported the highest age adjusted incidence rate (AAR) among males  with highest cumulative risk of 1 in 69 men developing HPV related cancers between 0 and 74 years, followed by Kamrup urban PBCR, Assam (AAR: 10.7) and Meghalaya state (AAR: 9.1). Papumpare district in Arunachal Pradesh showed highest incidence  among females, with lowest being Dibrugarh district, Assam . The risk of developing HPV related cancer was lowest in Sikkim state among males (cumulative risk: 1 in 749) and Dibrugarh district among females (cumulative risk: 1 in 133) .Nine out of ten HPV related cancers were cervical cancers in India . PapumpaOropharyngeal cancer was the most common among HPV related cancers in males (63.2%). Among females, they constituted 3.6% to HPV related cancers in India  to total cancer cases in India. The leading HPV related sites would be oropharynx (60.6%), followed by penis (26.3%) among males and cervix uteri (88.4%) among females. The remaining sites, namely, anus & anal canal, vulva and vagina together would constitute 11%–13% of total HPV related cancers .This comprehensive study provides the incidence rates, cumulative risk, clinical extent of disease, treatment modality, histological classification of HPV related cancers in India from a large network of cancer registries. The study showed that cervical and oropharyngeal cancers were the most common HPV related cancers among females and males, respectively, in India. These cancers together contributed around 85.0% of total HPV related cancers.Cervical cancer incidence was higher among PBCRs in north eastern region of India. However, its incidence rate showed a decreasing trend among most of the PBCRs over time . The stuA combination of radiotherapy and chemotherapy treatment was advised irrespective of the stage of disease with varied proportions of surgery. The treatment pattern observed in this study aligned with the existing evidence –23. A muThe study found that six out of ten HPV related cancers among males were oropharyngeal cancers in India. A global study in 2017 attributed 22.0%  CI: 5.0–44.0) of oropharyngeal cancer incidence in India to HPV infection –33. RepoVulval and vaginal cancers are rare cancers that showed minor decline in incidence for longer term in India . HPV infPenile and anal cancer together constitutes 1.2% of total cancer cases in India. Globally, more than half (51.0%) of the penile cancers were attributed to HPV infection with PAF ranging between 47.0% and 55.0% . This inHPV vaccines were licensed in 2008 for adolescent girls in India to be used on prescription base. Further, efforts were taken through demonstration vaccination projects, opportunistic screening and population-based screening –47. HoweThe main strength of the study is the use of high-quality data from HBCRs and PBCRs under the NCRP that are spread across the country. The data were abstracted from multiple sources such as cancer care hospitals, laboratories, and vital statistics departments using well trained registry staff, and cleaned using a robust quality check mechanism. Although the NCRP provides reliable information on incidence and treatment of malignant cancers related to HPV, they do not collect data pertaining to HPV genotype status and other risk factors.One out of 13 cancers in India is from HPV related sites. Implementation of effective prevention and control strategies like HPV vaccination and scaling up of screening, risk factor reduction could reduce the burden of HPV related cancers. Evidence from the NCRP serves as the baseline to monitor the impact of HPV policies and programmes in improving the outcome and prognosis.AAR, Age adjusted incidence rate; APC, Annual percentage change; CR, Crude incidence rate; HBCR, Hospital Based Cancer Registry; HPV, Human papillomavirus; IARC, International Agency for Research on Cancer; ICMR, Indian Council of Medical Research; NCDIR, National Centre for Disease Informatics and Research; NCRP, National Cancer Registry Programme; PBCR, Population Based Cancer RegistryThe authors declare no conflicts of interest.The authors received no financial support for authorship of this article.Thilagavathi Ramamoorthy: Conceptualisation, methodology, formal statistical analysis, writing – original draft, review and editing. Sathish Kumar Krishnan: Methodology, formal statistical analysis, data curation, writing – review and editing. Priyanka Das: Data curation, interpretation, writing – review and editing. Kondalli Lakshminarayana Sudarshan: Data curation, interpretation, writing – review and editing. Prashant Mathur: Conceptualisation, methodology, investigation, writing – review and editing, visualization, supervision, project administration. All authors have read and provided approval to the final version of the manuscript. The work reported in the paper has been performed by the authors, unless clearly specified in the text.This study was approved by the Institutional Ethics Committee of ICMR-NCDIR. Approval no: NCDIR/IEC/ 3052/2022.


Span-80 (2.0 g (4.67 mmol))-stabilized HIPEs were polymerized at 60 °C using potassium persulfate  as the initiator. Upon varying the volume ratio of aqueous calcium chloride from 80 to 90%, the prepared polyHIPE monoliths have shown significant variations in their surface morphology, specific surface area (SA), and pore volumes (Vp) as confirmed by scanning electron microscopy (SEM) and a gas adsorption (BET) method. The prepared polyHIPE monoliths were anchored with o-hydroxynaphthaldehyde propylenediamine Schiff base ligand (HNPn) and then loaded with copper(ii) ions (HNPn–Cu) to act as a catalyst. The structural information of unsupported HNPn–Cu complexes was obtained by recording its FT-IR and UV-visible spectra. The amount of copper(ii) ions loaded onto HNPn ligand-anchored polyHIPE monoliths was determined by atomic absorption spectroscopic analysis. In comparison to unsupported HNPn–Cu catalyst, the polyHIPE monolith-supported HNPn–Cu catalyst has shown high catalytic activity (66.8%), product selectivity for epoxycyclohexane (ECH) (94.8%), high turn over number (0.028 mol mol−1 h−1) and low energy of activation (22.4 kJ mol−1) in the epoxidation of cyclohexene in the presence of hydrogen peroxide (H2O2) as an oxidant at 40 °C. The polyHIPE-supported HNPn–Cu catalyst also shows high reuse applications. Studies show that there is sufficient scope to develop polyHIPE monoliths with various properties for specific applications.Poly(vinylbenzyl chloride- High internal phase emulsion of vinyl benzene and divinyl benzene in aqueous calcium chloride produced porous monoliths,which improved the activity of supported HNPn-Cu catalyst in selective oxidation of cyclohexene in presence hydrogen peroxide. Nevertheless, these methods remained ineffective in adding inter pore connectivity in porous supports26 and were not able to develop well-resolved surface pore morphology.25 Thus, highly inter-connected porous polymer monoliths are developed via the polymerization of surfactant-stabilized27–32 high-internal-phase emulsions (HIPEs) with a volume ratio of dispersed phase of >74%.33,34 The polymerization of HIPEs led to the formation of open-cell-structured macro-porous polymer monoliths with sufficiently high surface area and low density.31,35,36 These emulsion-templated, interconnected, and open-cell-structured highly porous monoliths29 are found to be useful in various applications such as supports for catalysts,6,37–41 recovery of residual oils,42 media for the storage of gases,43 or as an ion exchanger for the separation of metal ions.21,44 The nanoparticles supported on polyHIPE monoliths are more efficient5,45 due to better flow and mass transport properties of monoliths,6,46–51 which is well suited for catalysis.52 The surface-functionalized porous polyHIPE monoliths are also found to be useful in solid-phase syntheses and as a reagent scavenger.53–55 Though complexes of metal ions on inorganic supports are used as catalysts in various reactions,56–58 polymer supports provide a better microenvironment to both reactants and catalysts.14,37 Studies have indicated that supported Schiff base complexes of transition metal ions were more catalytic in the epoxidation of olefins59,60 than the unsupported ones.61,62 To utilize the properties of polyHIPE monoliths, some studies were conducted using physically63 or chemically bound catalysts on porous polyHIPE monoliths.37,63–66 However, chemically bound catalysts were found to be more efficient and useful as they are free from leaching problems and can be recovered from the reaction mixture. The epoxidation of olefins is a useful process as it can produce intermediates that find potential applications in the synthesis of fine chemicals, and in the production of useful polymers and pharmaceuticals. Though the epoxidation of olefins is possible with organic peroxides or hypochlorites, H2O2 reduces the formation of unwanted low-valued hazardous waste products. Thus, H2O2 alone or in combination with molecular oxygen/air is found to be more useful in the epoxidation of alkenes without any environmental problems. The epoxidation of cyclohexene using polymer-supported catalysts has been reported previously,67–69 but the epoxidation of cyclohexene using porous polyHIPE monolith-supported Schiff base complex of copper(ii) ions in the presence of hydrogen peroxide as an oxidant has not been reported yet. Thus, in these studies, attempts were made to develop porous polyHIPE monolith-supported copper(ii) ion complex of o-hydroxynaphthaldehyde propylenediamine Schiff base ligand (HNPn) as a catalyst for the epoxidation of cyclohexene in the presence of H2O2 as an oxidant.37,63 The complexation of copper(ii) ions for the epoxidation of cyclohexene was carried out using HNPn ligand-functionalized polyHIPE monoliths of different porosities.70,71 The pore size and porosity of the prepared polyHIPE monoliths were controlled with different volume ratios of aqueous calcium chloride in high-internal-phase emulsions (HIPEs). The polymerization of HIPEs at 60 °C in the presence of potassium persulfate (K2S2O8) has produced interconnected porous polyHIPE monoliths with uniform morphology as determined by scanning electron microscopy (SEM). To improve the properties of polyHIPE monoliths, hyper cross-linking in polyHIPE monoliths was carried out using dimethoxymethane as the external cross-linker.72,73In recent years, the development in synthetic chemistry has taken place at an alarming rate using various types of supported catalysts.22S2O8), calcium chloride dihydrate (CaCl2·2H2O), methanol, and Span-80 (sorbitan monooleate) (HLB = 4.3) were purchased from Sigma Aldrich Chemical Company, USA. All other chemicals were used as received and deionized H2O (18.2 mU cm) was obtained using a Millipore Milli-Q Plus water system. The oxidation products of cyclohexene were determined using chlorobenzene as an internal standard and analyzing the reaction mixture using a gas chromatograph equipped with a capillary column  and a FID detector.Vinylbenzyl chloride (VBC), divinyl benzene , potassium persulfate (K2.1ii) ions, firstly, o-hydroxynapthaldehyde propylenediamine Schiff base ligand (HNPn) was prepared by taking the alcoholic solution of o-hydroxynapthaldehyde  and 1,2′ propylenediamine  in a Soxhlet apparatus. The solution was refluxed for about 45 min at 60 °C and then the resultant HNPn ligand was separated after cooling the extract. The separated HNPn ligand (Scheme S1aMw 382.642 mol−1) of HNPn ligand with 20 mmol of sodium nitrite (1.06 g) in 100 mL (1 N) hydrochloric acid at a low temperature propylenediamine (Scheme S1bMw 440.642 g mol−1) of nitrosated HNPn ligand in 50 mL (1.0 N) hydrochloric acid in the presence of metallic iron as a catalyst, which on reduction produced N,N′-bispropylenediamine Schiff base ligand (AHNPn) as shown in Scheme S1c.ii) ions, 5.0 g HNPn ligand-functionalized polyHIPE monoliths (polyHIPE-L) were added to an aqueous solution of CuCl2 . PolyHIPE monoliths prepared with different volume ratios of aqueous calcium chloride were functionalized with HNPn ligand (polyHIPE-L) using the same procedure and loaded with copper(ii) ions. To study the effect of meso- and microporosity of polyHIPE monoliths, the HNPn-supported polyHIPE-90 monoliths (polyHIPE-90-L) were hyper cross-linked with dimethoxymethane in the presence of ferric chloride (2.5 g) as a catalyst with 1,2-dichloroethane (50 mL)-swollen polyHIPE-90-L monoliths for 12 h. The HNPn ligand-anchored hyper-cross-linked polyHIPE monoliths (hp-polyHIPE-90-L) were subsequently loaded with copper(ii) ions (hp-polyHIPE-90C).To prepare polyHIPE-supported HNPn Schiff base ligand complex of copper(Scheme S1. After 32.2PolyHIPE monoliths were characterized for the surface morphology and pore size variation by recording their scanning electron micrographs (JEOL JSM 5610 LV). To record scanning electron micrographs, polyHIPE monoliths were attached securely on Al stubs using a double-sided carbon adhesive tape and sputtered with a 10 nm layer of gold.2 gas and using the Brunauer–Emmett–Teller (BET) model. The adsorbed volume of N2 at a relative pressure (P/P0) of 0.97 was used to calculate the total pore volume of the prepared polyHIPE monoliths. The porosity (ε) of polyHIPE monoliths was determined using the following equation  and dried (Vd) polyHIPE monoliths.The surface area of polyHIPE monoliths was determined by studying the adsorption of Nequation :1where Δ2.3ii) ion complex (HNPn–Cu) were recorded using a PerkinElmer 1600 FT-IR Spectrophotometer and a Shimadzu 1601 PC UV-visible Spectrophotometer. Elemental analysis of polyHIPE-L monoliths was carried out using a Haraeus Carlo Ebra 1108 Elemental Analyzer to calculate the loaded amount of HNPn ligand on polyHIPE monoliths. The loaded amount of copper(ii) ions on polyHIPE-L monoliths was estimated by determining the remaining amount of copper(ii) ions in the loading solution using an atomic absorption spectrometer (PerkinElmer 3100) at the λmax of copper(ii) ions. The molecular weights of HNPn ligand and its complex with copper(ii) ions were determined using a Vapor Pressure Osmometer  using dimethyl formamide as the solvent and benzyl as the standard. The magnetic moment (μ) of HNPn–Cu complex was measured using a vibrating sample magnetometer (VSM-155).FT-IR and UV-visible spectra of unsupported HNPn ligand and its copper(2.4ii) ions complex as a catalyst in the epoxidation of cyclohexene, 1.g of polyHIPE-supported HNPn–Cu catalyst was placed in a two-necked round-bottom flask containing 2.0 mL acetonitrile, and an equimolar amount (0.05 M) of cyclohexene and hydrogen peroxide (30 wt%) was added. The percent conversion of cyclohexene and product selectivity for epoxycyclohexane (ECH) was evaluated at 40 °C by analyzing the reaction mixture at different time intervals using a gas chromatograph. The epoxidation of cyclohexene was studied using polyHIPE monoliths of different porosities and using different concentrations of cyclohexene, an oxidant (H2O2), and polyHIPE monolith-supported HNPn–Cu catalyst. The epoxidation of cyclohexene was also studied by varying the reaction temperature from 30 to 50 °C and in the presence of unsupported HNPn–Cu complex as the catalyst. To determine the reuse applications of polyHIPE monolith-supported HNPn–Cu catalyst, the conversion of cyclohexene was also determined using recycled unsupported and polyHIPE monolith-supported HNPn–Cu catalyst.To evaluate the catalytic activity of polyHIPE monolith-supported HNPn–Cu ions was prepared and used to catalyze the epoxidation of cyclohexene, which is not yet reported in the literature. Various properties of polyHIPE monoliths such as porosity, pore volume, and high surface area53,73 were found to be useful in controlling the percent conversion of cyclohexene and the product selectivity of epoxycyclohexane on using polyHIPE monolith-supported HNPn–Cu catalyst. PolyHIPE monoliths have an increasing effect on the activity of supported HNPn–Cu catalyst and increased reuse applications.75,76The porous polyHIPE monoliths obtained from high-internal-phase emulsions (HIPEs) are able to overcome the channel-flow problem usually encountered with polymer gel-beads in continuous flow reactors.3.12 g−1) as determined by the BET method  with a 90% volume ratio of aqueous calcium chloride has produced polyHIPE monoliths (polyHIPE-90) with a porosity of 82.4% along with the pore opening (8–12 μm) at their surfaces . In compT method . The apprographs  and alsorographs .Vp), and porosity (ε) was observed  in the prepared polyHIPE monoliths. This suggested that during the polymerization of HIPEs, the activity of vinylbenzyl chloride and divinyl benzene monomers did not vary in reaction mixture and both were consumed in a weight ratio of 6 : 4 to produce polyHIPE monoliths with a fixed composition and uniform surface morphology .This has also suggested that hydrophilic and lipophilic balance (HLB) of Span-80 was sufficient to stabilize the aqueous-phase droplets in HIPEs prepared by varying the volume ratio of aqueous phase from 80 to 90%.co-divinyl benzene) copolymers in HNPn ligand-anchored polyHIPE-90 monoliths. However, the pore opening at the surface of hp-polyHIPE-90 monoliths was not sharp (2 g−1) and porosity (82%) in comparison to other polyHIPE monoliths (co-divinyl benzene) copolymers in HNPn ligand-anchored polyHIPE-90 monoliths were used up by adding a dimethoxymethane cross-linker.The hyper cross-linked polyHIPE-90 monoliths (hp-polyHIPE-90) were found to be meso- and microporous  due to aot sharp  as was sot sharp , which wonoliths  and 2. T3.2ii) ions loaded polyHIPE monoliths were prepared by reacting HNPn ligand-anchored polyHIPE monoliths with copper(ii) ions. For anchoring the HNPn ligand on polyHIPE monoliths, first of all, HNPn ligand was prepared by reacting o-hydroxynapthaldehyde and 1,2′-propylenediamine  scale" fill="currentColor" stroke="none"><path d="M0 440 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z M0 280 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z"/></g></svg>N and –C–O groups in the FT-IR spectrum of HNPn ligand  was confirmed by its FT-IR spectrum, which shows absorption bands corresponding to –CN (1635 cm−1) and –C–O (1297 cm−1) groups beside a broad band between 3100 and 3150 cm−1 corresponding to the primary amine (–NH2). The AHNPn ligand was anchored on polyHIPE monoliths (Scheme S2The copper(n ligand  has suppn ligand  correspoScheme S2. PolyHIPScheme S2 though aii) ions with HNPn ligand was confirmed from the observed shifts in absorption bands from 1635 cm−1 to 1617 cm−1 (–CN) and from 1297 cm−1 to 1329 cm−1 (–C–O) in the FT-IR spectrum of copper(ii) ions complexes of HNPn ligand  ions with HNPn ligand (ii) ions with HNPn ligand (ii) ions with HNPn ligand (ii) ions loaded onto unsupported and polyHIPE monolith-supported HNPn ligand was estimated by analyzing the loading solution  using an atomic absorption spectrometer . In comparison to polyHIPE-supported HNPn ligand, unsupported HNPn ligand has shown high complexation of copper(ii) ions (2.34 mmol g−1) as shown in μ) of HNPn ligand complex of copper(ii) ions (1.76 BM) has suggested a square planar geometry for HNPn ligand complex of copper(ii) ions (Scheme S3ii) ions on polyHIPE monoliths (ii) ions (1.19 mmol g−1) than polyHIPE-90 monoliths (1.17 mmol g−1) due to better opportunities for the binding of copper(ii) ions with HNPn ligand supported on hp-polyHIPE-90 monoliths (The complexation of copper(n ligand . The appn ligand . Similarn ligand . The appn ligand . The amoScheme S3. The varonoliths  was due onoliths . In componoliths .3.3−) via the interaction of hydrogen peroxide and HNPn–Cu catalyst was presumed to be more prominent than the unsupported HNPn–Cu catalyst (−) was presumed to involve in the formation of a transient intermediate (M–HNPn–CH–OOH−) upon interaction with cyclohexene (CH) through a dynamic equilibrium (K) with active species (M–HNPn–OOH−). The value of rate constant (k1) for the formation of active species via the interaction of HNPn–Cu catalyst and H2O2 on polyHIPE monoliths is assumed to be quite higher than that of the unsupported HNPn–Cu catalyst. The high value of k1 might be responsible to enhance the dynamic equilibrium (K) between active species (M–HNPn–OOH−) and transient intermediate (M–HNPn–CH–OOH−) on polyHIPE monoliths. The high value of equilibrium constant (K) on polyHIPE monoliths (k) to cyclohexene in the selective production of ECH in comparison to the formation of other reaction products such as CHOL, CHDOL, and CHON  and the reaction products were analyzed by gas chromatography. In comparison to unsupported HNPn–Cu catalyst, the polyHIPE monolith-supported HNPn–Cu catalyst was found to be more active and selective for epoxycyclohexane (ECH) than other reaction products such as 2-cyclohexene-1-ol (CHOL), 1,2-cyclohexanediol (CHDOL), and 2-cyclohexene-1-one (CHON). The activity of HNPn–Cu catalyst on polyHIPE monoliths was assumed to be like enzymes and the polyHIPE monolith-supported HNPn–Cu catalyst has shown high activity in the conversion of cyclohexene and the selective production of ECH in comparison to unsupported HNPn–Cu catalyst. Thus, considering the enzymatic action of HNPn–Cu catalyst on polyHIPE monoliths, the formation of active species  for its decomposition to form ECH in comparison to the decomposition of an intermediate on unsupported HNPn–Cu catalyst. Thus, the microenvironment provided by polyHIPE monoliths might be a significant factor that increased the activity of HNPn–Cu catalyst on polyHIPE monoliths in the epoxidation of cyclohexene in comparison to unsupported HNPn–Cu catalyst  has followed a route that increased the selective production of ECH for the transfer of oxygen , 2-cyclohexene-1-one (CHON), 2-cyclohexene-1-ol (CHOL) and epoxycyclohexane (ECH) , but on f oxygen . In compf oxygen , Table 42 g−1) that reduced the loading of copper(ii) ions in comparison to polyHIPE-90 or polyHIPE-85 monoliths. Initially, the percent conversion of cyclohexene was high in the presence of unsupported and polyHIPEs monolith-supported HNPn–Cu catalyst, but after a reaction time of about 100 minutes, the rate of percent conversion of cyclohexenes became slow due to a significant decrease in the remaining amount of cyclohexene and oxidant in the reaction mixture (−1 h−1) for HNPn–Cu catalyst supported on polyHIPE-90 monoliths in comparison to other types of polyHIPE monoliths and unsupported HNPn–Cu catalyst  and the energy of activation (Ea = 12.3 kJ mol−1) in the conversion of cyclohexene on using hp-polyHIPE-90 monolith-supported HNPn–Cu catalyst have suggested that cyclohexene was having proper orientation on hp-polyHIPE-90 monoliths in comparison to other types of polyHIPE monoliths and unsupported HNPn–Cu catalyst (ii) ions that were essentially needed to catalyze the conversion of cyclohexene. In comparison to unsupported HNPn–Cu catalyst, a large fraction of HNPn–Cu catalyst on polyHIPE monoliths was accessible to catalyze the conversion of cyclohexene and the selective production of ECH.Though the activity of HNPn–Cu catalyst supported on polyHIPE monoliths was found to be better than that of unsupported HNPn–Cu catalyst, the activity of HNPn–Cu catalyst supported on hyper-cross-linked polyHIPE monoliths (hp-polyHIPE-90) was found to be significantly high in the percent conversion of cyclohexene, selectivity for ECH, and TON . This hacatalyst  and 4. T2O2 from 0.5 to 2 at a constant molarity (0.05 M) of cyclohexene and the catalyst in the reaction mixture. The trend of the percent conversion of cyclohexenes  in the reaction mixture constant  of hydrogen peroxide and HNPn–Cu catalyst. The results have indicated that the percent conversion of cyclohexene increased linearly on increasing the molar ratio of cyclohexene from 0.5 to 1.0 on using unsupported and polyHIPE monolith-supported HNPn–Cu catalyst Fig. S1,Table 5. s Fig. S2 and its  Fig. S1,Table 5.  Fig. S3,Table 6. −) in the selective formation of ECH  and reaction intermediates (M–HNPn–CH–OOH−) in the reaction mixture  upon increasing the reaction temperature beyond 40 °C. The variation in the reaction rate (k) on varying the reaction temperature was used to calculate the energy of activation (ΔEa) for the conversion of cyclohexene, which was found to be low for polyHIPE-supported HNPn–Cu catalyst and also showed dependence on the type of polyHIPE monoliths used for supporting the HNPn–Cu catalyst. The comparison of change in entropy (ΔS), equilibrium constant (K), and energy of activation (ΔEa) for the conversion of cyclohexene has provided a concrete proof that polyHIPE monoliths were able to provide a suitable microenvironment to the supported HNPn–Cu catalyst to catalyze the conversion of cyclohexene and the selective production of ECH in comparison to the unsupported HNPn–Cu catalyst  remained almost 99% to its original activity on recycling it for about 8 times, whereas the HNPn–Cu catalyst supported on polyHIPE-90 monoliths was able to show almost the same activity after recycling for six times  ions to act as a catalyst (HNPn–Cu) for the epoxidation of cyclohexene in the presence of hydrogen peroxide as an oxidant at 40 °C. The polyHIPE monoliths prepared using 90% volume ratio of aqueous calcium chloride (polyHIPE-90) were having high surface area, porosity, and capability to load high amounts of copper(ii) ions in comparison to polyHIPE monoliths prepared with 85% (polyHIPE-85) or 80% (polyHIPE-80) volume ratios of aqueous calcium chloride. The polyHIPE monolith-supported HNPn–Cu catalysts were found to be highly active in the conversion of cyclohexene and in the selective formation of epoxycyclohexane (ECH) as confirmed from the obtained values of equilibrium constant (K), turn over number (TON), and energy of activation (Ea). The activity of polyHIPE monolith-supported HNPn–Cu catalyst was explained by proposing a scheme similar to the activities of enzymes. The percent conversion of cyclohexene and the selectivity for ECH were found to vary significantly on varying the molar ratio of HNPn–Cu catalyst and reaction temperature, but the selectivity for ECH remained almost constant on varying the molar ratio of cyclohexene and H2O2 in the reaction mixture. These trends have suggested that the conversion of cyclohexene and the selectivity for ECH was influenced significantly by the microenvironment of polyHIPE monoliths that modified the interactions of the supported HNPn–Cu catalyst with cyclohexene for its conversion and product selectivity of ECH in comparison to the unsupported HNPn–Cu catalyst. The polyHIPE monoliths helped in increasing the stability and reuse application of supported HNPn–Cu catalysts. These studies have clearly indicated that porous polyHIPE monoliths are very useful in modifying the activity of catalyst and have sufficient scope in catalysis and other applications.High-internal-phase emulsions (HIPEs) have been prepared at room temperature by vigorously stirring different volume ratios of aqueous calcium chloride (80–90%) in an organic phase containing a fixed amount of vinylbenzyl chloride (VBC) and divinylbenzene (DVB) in the presence of Span-80. The polymerization of HIPEs with different volume ratios of aqueous calcium chloride in the presence of potassium persulfate as an initiator at 60 °C has produced polyHIPE monoliths with different surface areas, pore volumes, and pore sizes. The polyHIPE monoliths have been functionalized with o-hydroxy napthaldehyde propylenediamine Schiff base ligands (HNPn) and then loaded with copper(Keerti Moghe and A. K. Sutar were research students at Department of Chemistry, IIT Roorkee and helped partly in collection of experimental data. The kinetics and characterization studies were carried out by Prof. K. C. Gupta during his visit to Department of Polymer Science and Engineering, Kyungpook National University, South Korea. Prof. Inn-Kyu Kang participated in discussions and improving the draft of this manuscript.The authors declare no competing financial interest.RA-009-C9RA05811G-s001


The human papillomavirus (HPV), commonly documented as the cause of warts, has gained much interest recently due to its possible links to several types of cancer. HPV infection is discussed in this review from multiple angles, including its virology, epidemiology, etiology, immunology, clinical symptoms, and treatment. Recent breakthroughs in molecular biology have led to the development of new methods for detecting and treating HPV in tissue. There is no cure for HPV, and although vaccines are available to prevent infection with the most common HPV viruses, their utilization is limited. Destruction and excision are the primary treatment modalities. This review sheds light on the epidemiology, molecular pathogenesis, the association of several other pathogens with HPV, the latest treatment strategies available to treat the same, and an overview of the progress made and the obstacles still to be overcome in the fight against HPV infection. The human papillomavirus (HPV), the most common sexually transmitted infection (STI), significantly negatively impacts a person’s social life. Sexually active people will get an infection at least once without developing any pathologies ,2. HPV iHPV infection is higher in developing countries. The combined studies of cytologically healthy women found that Sub-Saharan Africa (SSA) (24.0%), specifically Eastern Africa (33.6%) and Latin America (33.6%), had a higher HPV prevalence than the rest of the world ,10,11,12Men have a global prevalence rate of genital HPV infection ranging from 3.5 to 45%, whereas women have a prevalence rate of 2–44%, with similar transmission rates. Anogenital HPV is primarily transmitted through sexual contact. According to a 2014 study, 9.0% of 4065 healthy men from Europe, America, Asia, and Africa had an HPV infection. Homosexuals and HIV-infected men are at higher risk of HPV anal infection, with a higher incidence rate (90%) than heterosexual men, whose risk of HPV infection is determined by the number of sexual partners ,17. FurtCutaneous warts (CWs) are caused primarily by the genera β and γ (HPV4 and 65), with sporadic contributions from the genera HPV2, 27, and 57, and HPV1 from low-risk oncogenic genital HPVs (LR-HPV), also known as cutaneous HPVs ,22,23. AThe viral antigens and host receptors interact at the molecular level to allow the virus to enter the undifferentiated epithelial cells. Structural studies have revealed L1-specific heparan-sulfate proteoglycan (HSPG) binding sites that are high in lysine (K), which is required for productive infection ,28. OnceEndocytosis allows the virus to enter the cell and travel inside small vesicles to the ER and Golgi. It undergoes a series of interactions and structural changes that will enable the viral genome to be released close to the nuclear membrane. Nuclear pores let the episomal viral genome enter the nucleus and begin viral replication. HPV replication requires epithelial cell differentiation. Indeed, the virus ensures its persistence and multiplication by affecting undifferentiated basal cells. The basal cells consistently provide sequential viral protein synthesis while dedifferentiating. As a result, viral replication (latent or active) will occur, increasing the risk of HPV infection and associated diseases ,32. As aSmall double-stranded DNA viruses with a diameter of 50–60 nm and no envelope are members of the Papillomaviridae family. The viruses’ 72 capsomeres are copies of pentameric monomers composed of five identical L1 proteins that anchor one L2 protein ,33,34. TChlamydia trachomatis. Additionally, C. trachomatis may enhance the risk of HPV infection and support viral persistence [Chlamydia obstructs HPV-induced processes, such as mismatch repair (MMR), that maintain cellular and genomic integrity in coinfections. During coinfections, inverse modulation of MMR is distinguished by distinct post-translational proteasomal degradation and E2F-mediated transcriptional regulation [The two most prevalent factors in sexually transmitted diseases worldwide are HPV and sistence . Chlamydgulation .Chlamydia superinfection of these cells reduces the E2F-mediated control of DNA repair pathways and quiescence [C. trachomatis induces different host cell transcriptional pathways, according to a global transcriptome study. The development of C. trachomatis is slowed by HPV E6E7 by preventing the RBs from re-differentiating into EBs and inducing persistence. Both pathogens upregulate the immune response mediated by tumor necrosis factor (TNF), while C. trachomatis explicitly induces the inflammatory response mediated by IL-17 and NF-kB signaling. Additionally, oxidative phosphorylation, RNA regulation, RNA processing, and elevated MAPK pathways are all significantly affected by chlamydia [Interestingly, despite causing DNA damage by producing reactive oxygen species , Chlamydiescence . HPV E6Ehlamydia .Td has several virulence factors, such as attaching to epithelial cells and extracellular matrix elements, releasing degrading enzymes, producing cytotoxic chemicals, activating host-derived tissue-destructive matrix metalloproteinases, and inhibiting local immunological responses ,44. CTLPAt the molecular level, HPV and HIV interact, and one can lead to an infection with the other. Both men and women are more likely to contract HIV if they have an HPV infection, and HIV-infected people have a higher risk of developing cancer and dysplasia from HPV due to immune system suppression . The humIn a study conducted in Romania’s southeast region, it was observed that the HPV infection is widespread among HIV-positive women and is correlated with factors like age at first sexual experience, several partners, CD4 count, vaginal candidiasis, as well as the Gardnerella infection . It is bNeisseria gonorrhoeae, is an obligate human pathogen [T. vaginalis infection is a frequent and possibly dangerous infection. Infection with this protozoa is increasingly understood to be linked to reproductive tract problems, such as post-abortal infection, post-cesarean infection, preterm birth, and premature rupture of membranes, in addition to reproductive tract discharge and discomfort [Trichomonas vaginalis and HPV infections are not notifiable. N. gonorrhoeae, C. trachomatis, T. vaginalis, and HPV were frequently discovered in 53% of female patients at an urban STD clinic in Mongolia, according to a study [N. gonorrhoeae, C. trachomatis, and T. vaginalis, with oncogenic genotypes being present in 44% of positive cases [C trachomatis and N gonorrhoeae [gonorrhea, chlamydia, or trichomonas infections. It is a high percentage, especially considering that traditional STIs increase the risk of HIV transmission [The pathogen that causes gonorrhea, pathogen . T. vagiscomfort . Trichom a study . HPV wasve cases . One stuorrhoeae . Withoutsmission .MicroRNAs (miRNAs), one of the many classes of biomolecules dysregulated by HPV, have recently emerged as essential carcinogenesis regulators that can regulate intricate processes like cancer metastasis. Multiple cellular miRNAs may have a part in the development of HPV-related cancer, according to in vivo research using mouse strains that are HPV-16 transgenic . High-riCompared to exosomes from HPV-negative cells, those from HPV-positive cells have better angiogenic potential and a higher rate of cellular uptake by endothelial cells. Increased expressions of PTCH1, VEGF-A, VEGFR2, and angiopoietin-2 are found when the underlying processes causing the angiogenic potential of HPV-positive exosomes are examined . In 2009De-intensification, or lowering the effects of the cancer therapy regimen in some way, is a hot topic in HPV-positive cancer research, although few de-intensification trials have been conducted in recent years. A study in 2017 conducted a phase II trial where they evaluated the complete clinical response towards induction chemotherapy to investigate whether they could select patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) for a reduced radiation dose, which might help in impeding the disease progression . This clThe incidence of HPV infections and the associated diseases keeps increasing. Advanced prevention strategies are required to eradicate viral infections. HPV is commonly transmitted sexually. About 300 million women are carriers of the HPV virus . Most HPAlthough there is no cure for HPV, cytologic testing has been essential in treating CC since the 1950s . To manaVaccines were developed to protect against HPV infection and the subsequent onset of HPV-associated disorders. Although three different vaccinations have been clinically produced, not all of them are readily available everywhere. These vaccines range in the number of HPV strains they can contain and target . The quaListeria, Shigella, Salmonella, and Lactococci have been extensively used to make the HPV vaccine [Leishmania tarentolae would be an effective vector for the delivery of the HPV16 L1 antigen and the induction of strong humoral immune responses, thus presenting a powerful immunization approach against HPV and other intracellular diseases [Prophylactic VLP (virus-like particles)-based vaccines have some disadvantages. These include the high cost and the presence of a suitable cold chain. These limitations have prevented its widespread usage in underdeveloped or resource-poor nations, where there were 80% of CC cases . As a co vaccine . The devdiseases .Salmonella, Lactobacillus lactis, and Listeria monocytogenes  are today’s most prevalent bacteria-based tumor immunotherapy vectors [Salmonella and Listeria against HPV, data have demonstrated a wide range of adverse effects for the latter, making lactic acid bacteria vaccinations an effective and promising alternative to the more common attenuated pathogenic bacterial vaccine [Due to their convenience and high immunogenicity, live bacterial vectors are used for therapeutic HPV vaccines and are one of the high-potential vector-based vaccines.  vectors . In prev vectors . Recent  vectors . When co vaccine .In order to deliver therapeutic genes to cells for human gene therapy, viral vectors have emerged as crucial tools . AdenoviPeptide-based vaccines, one of the most influential vaccine platforms, have received significant research attention as no vaccines have been efficient enough to eradicate pre-existing HPV infections. With the help of non-auto immunogenic antigen sequences derived from cancer-associated proteins, peptide-based vaccines can stimulate cellular immune responses and eradicate CC . PeptideHuman immunodeficiency virus (HIV) patients are treated with anti-HIV medications as part of antiretroviral therapy (ART). The recommended course of treatment includes a cocktail of medications that prevent HIV replication, frequently referred to as “highly aggressive antiretroviral therapy” or HAART . HAART cListeria monocytogenes (Lm) is most well-known for its capacity to infect people and cause a range of symptoms, which includes gastroenteritis, meningitis, and encephalitis [The Gram-positive bacteria phalitis . Listeriphalitis . Increasphalitis .A virulence component in the Lm life cycle, called listeriolysin O (LLO), pierces the phagosome to facilitate Lm entrance into the cytosol. A study of efficient antitumor immunity employing tLLO-TAA (Truncated LLO- tumor-associated antigens) structures reported that mice injected with HPV LLO-E7-expressing Lm had a complete regression of almost 75% of cancer .In terms of sexually transmitted diseases, HPV ranks the highest. CC is the most devastating health effect of an HPV infection. In contrast, malignancies caused by human papillomavirus (HPV) also account for a considerable portion of male mortality and morbidity. Further research is needed to understand the course of oral HPV infection more fully. Regular screening for HPVis neither practical nor feasible. Efficacy against prolonged cervical infections, and in the case of the qHPV vaccine, efficacy against anal infections, has been demonstrated for all three preventative HPV vaccines. Campaigns to prevent the spread of human papillomavirus (HPV) should prioritize vaccinating against high-risk and low-risk strains of HPV and reducing the prevalence of HPV disease in people who have previously been exposed to the virus. In recent decades, much progress has been made in understanding how HPVs engage with host cells, tissues, and the immune system. In order to prevent HPV infections, studies have verified and deployed safe and effective prophylactic immunization techniques. An increasing number of people know about HPV and the myriad problems it can cause in women, men, and children; research has also improved the sensitivity and specificity of molecular diagnostic methods for HPV identification that can be used in CC screening. While these successes demonstrate the power of biomedical research to generate vital public health interventions, they also create new and daunting challenges, such as the high price tag associated with HPV prevention and treatment, the difficulty of putting into practice what is technically feasible, the social and political opposition to preventative measures, and the wide variation in economic and health care infrastructure between countries.


Objective: Cervical cancer is a serious potential risk to women’s health, and is closely related to persistent HPV infection. Vitamin K mainly existed in green vegetables, fruit, and dairy products. This research aims to observe the association between vitamin K and HPV-infection.Methods: 13,447 participants from the NHANES were selected. Dietary vitamin K intake was used as the objective independent variable and continuous variable, HPV-infection status was used as the outcome variable, and characteristics of selected participants were used as the covariates.Results: There was a nonlinearity between vitamin K intake and HPV-infection, and the inflection point is 3.81 of log2 vitamin K intake. In a range of 0–3.81, Each one-unit increase in log2 vitamin K intake was associated with a 43% reduction in the risk of HPV infection. When log2 vitamin K intake excess of 3.81, the risk of HPV infection did not continue to decline. The HPV-subtype was not associated with vitamin K intake.Conclusion: There is a nonlinearity between vitamin K intake and HPV-infection status. But HPV-subtype was not associated with vitamin K intake. Cervical cancer is a serious potential risk to women’s health, and most occurrence remains in almost all low-income countries due to the lack of diagnostic technologies . CervicaThe vitamin K family consisted of a 2-methyl-1,4-naphthoquinone ring structure, which is naturally containing vitamin K1 and vitamin K2 . VitaminRecent studies show that persistent HR HPV-infection is not only a risk factor for cervical cancer, but also includes dietary nutrient intake , 28. Morhttps://www.cdc.Gov/nchs/nhanes/about_nhanes.htm). The Ethics statement of the observational study was approved by National Center for Health Statistics (NCHS). The Institutional Review Board Approval was available on the official website of the Centers for Disease Control (https://www.cdc.gov/nchs/nhanes/about_nhanes.htm).All the participants in this analysis were selected from the NHANES, which is a cross-sectional investigation of nutrition and health in the population of the United States of America. It is a continuous public database, with nearly 5,000 people accessed yearly. The participants during 2003–2016 of the NHANES, who meet the analysis criteria were selected . The parhttps://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx). Moreover, vitamin K intake was also used as the continuous variable in this analysis.In this analysis, the independent variable was dietary vitamin K intake. This data is obtained by an average of the dietary vitamin K intake of the participants on the first and second days from the NHANES database. The detail of measurement was available on the NHANES official website . Meanwhile, HPV subtypes were also recorded as a dichotomous variable . HPV infection was tested by HPV DNA genotyping assay, and the detail of the process of HPV testing was available on the NHANES website.Based on the factors associated with HPV-infection that are reported in the previous study –43, we up < 0.05 was considered statistically significant.The objective of this study was to assess the risk of vitamin K intake on HPV-infection. This study was a cross-sectional observation without exploring causality. The clinical characteristics of participants without HPV-infection records were roughly the same as those with the HPV-infection records. So there is no bias in the analysis. Depending on whether continuous variables are normally distributed, the continuous variables are represented as mean  or median . Vitamin K intake was acted as a grouping variable  to describe the study population. The 4 groups were assessed with One-way ANOVA  or Kruscka Whallis-H (skewed) to evaluate the differences between groups of continuous variables. The differences between groups were evaluated by a rank-sum test. p-values. Since the independent variable in this study is a continuous variable, we conducted the data following sensitivity analysis: 1) the continuous variable was entered into the model to calculate the effect value; 2) the disordered classification variables have entered into the model to observe the effect value; 3) The ordered classified variables were put into the model to calculate the tendency test.The data on dietary vitamin intake showed skewed distribution in the participants, so we process vitamin intake with log2 transformation. Results of data analysis were presented in three models: Model 1 (non-adjusted model); Model 2 ; Model 3 . Adjusted covariates included in Model 3 were screened based on confidence intervals  and odds ratios (OR), but not based on univariate analysis p-value, the best fitting model was constructed. If p-value ≤ 0.05, there was a nonlinearity between vitamin K intake and HPV-infection, otherwise, linearity appeared.All the covariables were adjusted using a generalized additive model (GAM) to assess the nonlinear relationship, and smooth curves were also plotted. When a nonlinearity was presented, we calculate the inflection point with a recursive algorithm. And then based on both sides of the inflection point, we constructed a piecewise linear model. At last, based on the logarithmic likelihood ratio test A total of 13,447 participants in the NHANES from 2003 to 2016 were selected for this analysis. Dietary vitamin K intake was acted as a grouping variable . Compared with the Q4 group, the participants in other groups  have higher BMI and are younger. Compared with Q1, participants in other groups  have more intake of vitamin B6, vitamin B12, vitamin C, folic acid, and dietary calcium. Moreover, no significant differences could be found among different dietary vitamin K intake groups in the number of sexual partners in the last 12 months. But there are significant differences among groups in race, education levels, marital status, smoking over 100, vaginal or anal intercourse times in last year, poverty income ratio, and HPV-infection.p-value in the three models are shown in To obtain the relationship between vitamin intake and HPV-infection status, three models are processed to investigate the trend of effect value (OR and 95% CI). The OR, 95% CI, and Based on Model 3 , smooth curve fitting showed a nonlinearity of dietary vitamin K intake with HPV infection , and theIt is reported that persistent HR HPV infection has been considered the risk factor for the development of cervical cancer . HoweverIn our study, there is a nonlinearity between dietary vitamin K intake and HPV-infection . In the 3.81 = 14.03) dietary vitamin K intake maybe reduce the risk of HPV-infection. Therefore, our results suggested a guideline of dietary vitamin K intake of more than 14.03 (23.81) mcg.In previous studies, diets containing vitamin B6, B12, C, and folic acid have been reported to prevent from HPV-infection , 30, sucThis analysis was processed with the following strengths. Firstly, the missing data of each covariate is non-randomly missing. So we proceed with dummy variables to adjust them, which could minimize the bias caused by missing variables. This method is usually applied for the observation of a large sample . SecondlHowever, there are still some limitations in our findings. Firstly, 13,447 participants are women aged 18–59 years from the NHANES database, so the results have restrictions on gender, ethnicity, age, geography, and some important covariables are not contained, such as whether HPV vaccine was injected or not. Secondly, our research is a cross-sectional study. We can not obtain the exact causal relationship between vitamin K intake and HPV-infection. Thirdly, dietary intake was obtained from “24-h dietary recall interviews” of NHANES participants. So, our research has some unavoidable weaknesses such as recall bias, measurement bias, and so on. Finally, in our study, we use regression equations to adjust the possible potential confounders, but there are still some unmeasurable confounders.We observed a nonlinearity of vitamin K intake with HPV infection. Each one-unit increase in log2 vitamin K intake is associated with a 43% reduction in the risk of HPV infection. When log2 vitamin K intake excess of 3.81, the risk of HPV infection did not continue to decline with additional increases in vitamin K intake. In addition, the HPV subtype was not associated with vitamin K intake.


In the US, incidence and mortality from cervical cancer disproportionately affects racial/ethnic minorities and low-income women. Despite affordable access to primary and secondary prevention measures at Federally Qualified Health Centers (FQHCs), Human Papillomavirus (HPV) vaccination and screening rates are low, suggesting the presence of non-financial barriers to uptake in this population. This explanatory sequential mixed-methods study sought to explore factors that influence the acceptability of cervical cancer prevention services among parents and legal guardians of vaccine-eligible girls attending an urban FQHC and to assess social influences related to cervical cancer prevention. Participants included eight mothers, one father, and two grandparents/legal guardians. Nine participants self-identified as Black/Afro-Caribbean, or African American, two as Latinx, and one as Native American. The quantitative data suggested discordance between participants’ cervical cancer prevention knowledge and their practices. Most indicated that their daughters had received the HPV vaccine but were unsure about HPV transmission modes. Qualitative data revealed that participants were comfortable disclosing information on HPV infection and vaccination status, and most women were likely to share information related to cervical cancer testing and diagnosis. Few comments indicated personal stigma on the part of participants, but there was frequent expression of perceived public stigma (shaming and blaming women), gender differences (men are indifferent to risk), and distrust of the healthcare system. Findings highlight several concepts including the disharmony between knowledge and practice, prevalent perceived public stigma, cumbersome attitudes on the part of men regarding HPV and cervical cancer, and distrust of the healthcare system. Cervical cancer is the second-leading cause of cancer deaths among U.S. women aged 20–39 years and disproportionately affects racial and ethnic minorities and low-income women . VaccinaStigma is a potent negative social influencer and is initiated and perpetuated by social structures and power dynamics that ascribe undesirable characteristics to particular conditions , 10. SocThis exploratory study took place at the Mile Square Health Center-Main (MSHCM) clinic in the city of Chicago. Affiliated with the University of Illinois at Chicago Hospital Health Sciences System, MSHCs are a group of 14 FQHCs serving more than 40,000 patients annually. We utilized an explanatory sequential  mixed-methods study design to identify potential trends in the data and to focus on the lived experiences of these study participants –23. QuanStudy participants were parents (mothers or fathers) or legal guardians of HPV vaccine-eligible girls  attending the MSHCM pediatric clinic. Study staff identified eligible participants from the clinic’s weekly schedule of incoming patients, and potential participants were contacted by phone and invited to participate in the study. Following completion of the informed consent process, participants received a secure electronic link to the self-administered survey using REDCap software. Study staff reviewed each participant’s completed survey and then scheduled a telephone interview. Semi-structured interviews were audio recorded and later transcribed verbatim. Participants received a $50 gift card. This incentive was approved by the IRB as adequate for the participants’ time without being coercive.Characteristics of the study population as well as knowledge, practices, and attitudes related to cervical cancer prevention were tabulated. Bivariate analysis was conducted to explore differences in the distribution of attitudes by women’s screening time (< 3 years vs. ≥ 3 years) to align with U.S. Preventive Services Task Force cervical cancer screening recommendations  and chilFor the qualitative data analysis, we used an inductive, iterative approach  using DeThe non-probabilistic sample included 11 participants—eight mothers, one father, and two grandparents/legal guardians. The mean age of participants was 43.1 years (SD = 9.4), and all women in the sample were eligible for cervical cancer screening. Racial/ethnic heritage were not mutually exclusive categories, and nine participants self-identified as Black/Afro-Caribbean, or African American, two as Latinx or Hispanic American, and one as Native American. More than half (55%) of participants had graduated from high school or received their GED certificate, and 45% had graduated from college or completed some college. The majority (64%) of participants were covered by Medicaid, three (27%) were covered by private insurance or a Marketplace Plan, and one had no health insurance. The majority (82%) of participants’ children were covered by Medicaid .The majority of participants reported that they have heard about and understand HPV (64%), cervical cancer (91%), the HPV vaccine (73%) and Pap test (100%). Most reported that their daughters had received the HPV vaccine (73%). However, there was some inconsistency between this practice and some aspects of participants’ knowledge. For example, only 27% of participants felt they understood how to protect their child from HPV very well and only 36% felt they understood the risks associated with HPV very well. Most participants were unsure how HPV is transmitted (55%) and whether it was likely that a diagnosis of HPV meant one could infect someone else (45%).Of the 10 women in the study, all were eligible for cervical cancer screening. Although eight women reported having had a Pap test, three reported receiving a test more than three years ago. There was some discordance between participants’ screening practices and their knowledge. Four of the eight women reporting past Pap tests felt that they understood how to protect themselves from cervical cancer, while two felt they did not and two were unsure .Most participants indicated that they would be likely to disclose information regarding their own (or their child’s) HPV status, as well as their child’s vaccination status. Similarly, most women were likely to share information related to cervical cancer testing, receipt of a positive Pap test, and a cervical cancer diagnosis with healthcare providers, a person close to them, and future sexual partners . When asSocial influences related to HPV and cervical cancer. Study participants tended to disagree with statements indicating discomfort with someone infected with HPV (45%) or with cervical cancer (73%). This pattern persisted with respect to avoidance and blame. Participants disagreed with statements that they would avoid someone with HPV (91%) or cervical cancer (100%). Similarly, participants did not fault others for their HPV infection (82%) or for developing cervical cancer (91%). However, when asked how likely it is for others within their social network to blame a person for their HPV infection, only 27% believed it was unlikely , gender differences (Men are indifferent to risk), institutional perception , and positive social influence (Influencing others through shared experiences).Perceived public stigma. Although participants seldom described experiences or feelings of personal stigma, there were numerous expressions of perceived public stigma related to HPV infection and cervical cancer diagnosis. Participants’ shared perceptions that members of their social networks blame women for their cervical cancer diagnosis. Furthermore, there is a sense within their communities that HPV infection is viewed as shameful. Participants also believed that men within their social networks do not acknowledge their role in a female partner’s HPV infection.Because it is something you live with the rest of your life, and it can be passed on or whatever. If you get it, the disclosure, having to disclose it with your partner, and the effects that it can take on a relationship if you had it, and all of that.”  Many participants also commented on “blame” toward women who have cervical cancer. Participants stated that others believe that these women must have "done something" to end up with this diagnosis. “They blame the women.”  It was stated that it “is the woman that gave it to the man.”  Another participant indicated blame in commenting that many people feel that there is a behavior that causes cervical cancer. It was stated that to avoid getting cervical cancer, you have to "keep your legs closed." It was also stated that, “In letting that person with the cervical cancer isolate themselves from them or distance themselves from them, because in their minds it’s maybe that it’s contagious.”  Regarding the perceptions of others, one participant expressed that there is a thought that "more conservative" women  were more judgmental. “I think it’s just because it’s cancer. When people hear the word cancer, they get nervous, they get cautious. They think is it contagious. They’re unaware, so they’re like, ‘We don’t know what’s going to happen.’ So they don’t want to come around.”  Participants further illustrated blame in stating that women who have cervical cancer or are HPV positive are “spoiled.”  “Yep. They nasty, or they sleep around, or they wild, or they out there not protecting themselves and not being cautious and just sleeping around.” Participants stated that people do not openly talk about HPV infection because there is shame associated with it. “Men are indifferent to risk. Participants expressed that men that they know do not take precautions against HPV and that men’s behavior is riskier than women’s. One participant stated that, “a lot of men can be degrading. A lot of men don’t care if they do have it. They will continue if it’s contagious or spreadable. Some men that I have known wouldn’t care. They would just spread it if they can or they would just not take it as serious as doctors, and women would take it seriously.”  In addition, this participant noted, “A woman that has cervical cancer, I believe that some men in my family members don’t take it seriously. They may have feelings about the situation but if it don’t concern them, they’re not interested. Or they’ll have less pity for them unless it’s their mother or a spouse.”  It is perceived that men judge women differently than other men. “It can be a double standard when it comes to something like that because [being infected with HPV is] not portrayed as a serious matter as far as it would be for a woman.”  Another participant remarked that among men there is blaming and shaming of the women who are HPV positive. It was stated that “they would single out more women than men”  when it comes to HPV infection. Finally, a participant stated, “I feel that a lot of men don’t have a lot of knowledge towards HPV, I think.” .Distrust of the healthcare system. Participants’ comments indicated that there was a pervasive distrust of the HPV vaccine, recommendations from doctors, and the healthcare system. One participant commented that, “I know some people don’t want to vaccinate because they feel like the cancer is in the vaccination.” (part. #6 mother) Another remark was that it was “Not trustworthy of the doctors. A lot of doctors are not good out here. Some doctors are in it for the money. And some doctors, in my way of life… by me being African American, it’s a stigma towards doctors that won’t treat African Americans as well as another race. So our stigma towards doctors are not well.”  Finally, it was pointed out that, “The relationship between doctors and patient in my society is not a great relationship. So a lot of times they will say, ‘Oh, your child needs a vaccine.’ But then again, you will hear negative things about the vaccine, maybe horrible side effects within that person. And it would discourage them from not wanting to treat that child or their self to get the vaccine.”  In addition, a participant discussed that having limited coverage by some insurance plans causes people to distrust the healthcare system. “Definitely. With my 23-year-old, she just feels like… She has to get her a better job where she can get better insurance because with public aide it’s just giving us the bare minimum insurance. She’s going through what I went through with these bacteria infections. I feel that a lot people just have lost trust in the system.” .Influencing others through sharing experiences. Participants reported that the sharing of personal stories regarding cervical cancer prevention is a good way to influence others to make similar choices. One participant stated, "I’m open to share it. They look at that and they take heed." It was also stated, “and then when I got my situation taken care of, I went back to work and I started talking about it, and it made two other coworkers… We’re all from the same neighborhood. Made them go and get they self-checked out.”  This same participant remarked that "I literally talked them into going and seeing about it" when discussing cervical cancer screening. A further comment was, “Actually I had a conversation with some of my family members about it and let them know that I did do that. And then I found out a lot of them got it too and had it for their young lady children as well.”  Finally a participant stated, “Because I feel confident about the decision. Now it might help another family, another parent. It may not, but still, I am going to share. Yeah.” Our findings from this explanatory sequential mixed-methods study highlight several concepts including the disharmony between practice and knowledge, prevalent perceived public stigma—including dismissive attitudes on the part of men regarding HPV and cervical cancer, distrust of the healthcare system, and the promise related to positive social influence.The first phase from quantitative data suggested possible discordance between participants’ cervical cancer prevention practices and their knowledge. Although most participants indicated that their daughters had received the HPV vaccine, they were unsure about HPV transmission modes. All the women in the study reported past receipt of a Pap test but not all had received a test within the past three years. We hypothesize that incongruence between practice and knowledge may result in inconsistent prevention behaviors such as guideline concordant screening.Regarding stigma, the qualitative data reinforced a common quantitative finding. Notably, participants themselves were comfortable disclosing information on HPV infection and vaccination status, and most women were likely to share information related to cervical cancer testing and diagnosis. While there were minimal comments expressing personal stigma on the part of participants, there was frequent expression of perceived public stigma. Participants did not stigmatize HPV and cervical cancer themselves however, this attitude did not extend to their social network—particularly with respect to HPV infection. Women participants’ expression of perceived public stigma indicates a fear of being discriminated against. This revealed that there is a view that others may hold prejudices toward women who are HPV positive or diagnosed with cervical cancer.The qualitative phase also expanded on the findings from the quantitative phase indicating gender differences, a distrust of the healthcare system, and indications of positive social influence related cervical cancer and HPV vaccination interpersonal communication. These data illustrated that responses from participants indicated differences in the way genders perceive and react to circumstances regarding cervical cancer and cervical cancer prevention. This suggests that there are direct and indirect differences in the way that women and men express their perceptions around HPV infection or a cervical cancer diagnosis, especially related to perceived public stigma, blame, personal responsibility, empathy, valuing prevention, and valuing reliable information. Our findings indicate that men’s attitudes and behavior may be indifferent to HPV risk. In addition, there is a perception that men may blame or shame women for a cervical cancer or HPV diagnosis.Many participants indicated that there exists a distrust of the healthcare system in their communities which is problematic for positive cervical cancer prevention behaviors. Participants hold a distrust of the HPV vaccine, itself, of the doctors who are recommending the vaccine, and of the healthcare system as a whole. There was an indication that the distrust is born through a generational conditioning. In particular, it is notable that participants stated that African Americans believe that doctors won’t treat African Americans as well as another race. This is consistent with findings from recent studies –34 and pThe qualitative analysis also illustrated that women often use their own experiences to influence the decisions of others. Participants expressed belief that this type of communication has a positive effect on the behavior of their peers. Individuals who have, themselves, taken action by getting screened for cervical cancer or having their daughter get the HPV vaccine may act as sources of positive social influence by sharing their decisions and experiences with others.These findings suggest that leveraging positive social influence may be a useful strategy to address identified perceived cervical cancer and HPV-related public stigmas, men’s indifference to HPV risk, and the existing distrust of the medical system. Positive social influence has been shown to influence the behavior of decision-makers –38 and mThis exploratory study begins to address an important gap in the literature defining the relationship between the effect of social influences on the acceptability of cervical cancer prevention and the hesitancy to seek these health services—particularly among those receiving care at FQHCs. Nevertheless, we acknowledge important limitations. The quantitative results are not hypothesis driven and unencumbered by power and sample size limitations however, inference and generalizability are limited and conclusions regarding the causal nature of these relationships cannot be established. Given the small sample size and minimal variation in vaccination and screening outcomes we were unable to examine the relationship between measures of social influence and these outcomes through multivariate models. Our results provide insight into the ways in which stigma, gender differences, and medical mistrust may negatively influence decisions related to cervical cancer prevention and suggest a path of further exploration to elucidate these relationships.Our findings illustrated various barriers to cervical cancer prevention with consistency between primary (HPV vaccination) and secondary  prevention as well as perceptions and attitudes regarding HPV infection and cervical cancer diagnoses. Future public health interventions should focus on a unified message to increase the understanding of the relationship between HPV and cervical cancer as well as the various modalities for the prevention of cervical cancer. Efforts should also focus on addressing men’s attitudes, in particular, regarding HPV and cervical cancer. Men’s attitudes as well as women’s perceived attitudes may contribute to our finding of perceived public stigma. More research should be conducted to better understand the relationship between this observable stigma and the practice of HPV vaccination and cervical cancer screening. It is likely that decision makers are discouraged from the uptake of cervical cancer prevention services due to these social factors. Our study also reinforces previous findings of distrust of the healthcare system, which adversely affects uptake. In addressing these critical issues, our findings suggest that interventions leveraging positive social influence may be a promising approach to addressing the identified barriers. In advancing the broader goal of the elimination of cervical cancer as a public health problem, robust research is needed to better understand the social phenomena that are directly related to factors influencing cervical cancer primary and secondary prevention.