Human papillomavirus (HPV-HR) infection of the cervix results in different manifestations of lesions depending on the immunologic capacity of the host. Variations in apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-like genes, such as the APOBEC3A/B deletion hybrid polymorphism (A3A/B), may contribute to cervical malignancy in the presence of HPV. The aim of this study was to investigate the association between the A3A/B polymorphism and HPV infection and the development of cervical intraepithelial lesions and cervical cancer in Brazilian women. The study enrolled 369 women, who were categorized according to the presence of infection and subdivided according to the degree of intraepithelial lesion and cervical cancer. APOBEC3A/B was genotyped by allele-specific polymerase chain reaction (PCR). As for the A3A/B polymorphism, the distribution of genotypes was similar between groups and among the analyzed subgroups. There were no significant differences in the presence of infection or development of lesions, even after exclusion of confounding factors. This is the first study to show that the A3A/B polymorphism is not associated with HPV infection and the development of intraepithelial lesions and cervical cancer in Brazilian women.The persistence of a high-risk  Human papillomavirus (HPV) infection of the cervix results in different outcomes depending on the type of virus, persistence of infection, and intrinsic immune properties of the host [A the host . Asymptothe host . Howeverthe host .Variations in the apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3)-like gene, such as the APOBEC3A and APOBEC3B deletion hybrid (A3A/B), may be associated with persistent viral infections and the establishment of the somatic mutations that predispose to cellular malignancies .The variant A3A/B allele is characterized by the deletion of 29,936 base pairs (bp) between the fifth exon of A3A and the eighth exon of A3B . It resuIncreased expression of the A3A protein encoded by the wild-type allele and/or the variant allele favors the formation of homodimers that tend to interact with specific sites (5’TC) in RNA or single-stranded DNA (ssDNA) ,10. The In cervical cancer, the variant A3A/B allele amplifies the somatic mutational burden caused by the virus, confirms the genomic instability of cervical cells, and increases viral diversity, leading to neoplastic changes in the cervix ,19. ConsThe aim of this study was to investigate the association between the A3A/B polymorphism and HPV infection, the development of cervical intraepithelial lesions, and cervical cancer.The State University of Londrina’s Institutional Human Ethics Committee in Paraná, Brazil, approved this study . Informed consent was obtained from all participants, and they were informed about the study’s purpose and procedures. Women who participated in this case-control study were recruited from public health services in Londrina-PR, Brazil. Samples were collected from a nonrandomly selected biobank of 700 women (obtained by convenience). A structured questionnaire was completed to gather sociodemographic, reproductive, and sexual behavioral data. Participants were categorized based on the presence or absence of HPV DNA, and cervical cytology results were obtained from medical records.®, Curitiba, PR, Brazil). The DNA concentration was assessed using a NanoDrop 2000c TM spectrophotometer , and purity was determined by the absorbance ratio at 260 nm and 280 nm.Cervical cell samples were collected using cytobrushes from cervicovaginal smear, and peripheral blood was obtained through venipuncture using anticoagulant tubes. Genomic DNA was extracted from cervical brushings using DNAzol  and from peripheral blood using the Biopur Mini Spin Plus Kit (BiometrixThe detection of HPV was performed using the MY09 (5′-CGTCCMAARGGAWACTGATC-3′) and MY11 (5′-GCMCAGGGWCATAA-YAATGG-3′) primers, which were specifically designed to amplify a conserved region of 450 base-pairs (bp) within the L1 gene of HPV . To ensuDifferentiation between alleles for the APOBEC3A/B polymorphism was performed by allele-specific PCR technique , using sp < 0.05.This study analyzed a population divided into two groups based on their HPV infection status: uninfected and infected. Infected patients were further categorized based on the severity of cervical lesions observed , high-grade intraepithelial lesion (HSIL), and cervical cancer) according to the result of cytological examination. The study then used the chi-square test or Fisher’s exact test, as appropriate, to analyze the relationship between socio-epidemiological variables and the infection, lesion, or cancer groups, and employed logistic regression to predict the influence of studied polymorphisms on the development of infections and lesions. Tests were conducted using SPSS statistics 22.0 software , with a significance level of n = 74), low-grade squamous intraepithelial lesions (LSIL) (n = 14), high-grade squamous intraepithelial lesions (HSIL) (n = 45), and cervical cancer (n = 69).The study population consisted of 369 women: 207 (61.1%) were positive for HPV DNA, and 162 (38.9%) were negative. The infected (HPV-positive) women were divided into groups with no lesions (p = 0.003), smokers (p = 0.009), with a monthly income ≤ 1 minimum wage (p = 0.028), who used contraceptives (p = 0.001) and preservatives (p = 0.01), and who had their first sexual intercourse at age 17 years or younger (p = 0.03).Sociodemographic data, sexual behavior, and reproductive data are shown in p < 0.001), smoking , educational status , and monthly income (p = 0.013), as shown in p < 0.001) and did not use preservatives (p = 0.032), as shown in In the association of squamous intraepithelial lesion extent with sociodemographic characteristics, a significant association was observed for age , heterozygous (ins/del), and homozygous for the variant allele (del/del). The electrophoretic profile for each of these variants is shown in p = 0.275), and there was also no significant association in multivariate logistic regression adjusting for age, smoking status, monthly income, contraceptives, preservatives, age at sexarche, and sexual partners.According to the data in p = 0.361) was found with polymorphism  .In this study, we investigated for the first time in a Brazilian sample the association between A3A/B deletion and HPV infection and the development of intraepithelial lesions and cervical cancer. We also confirmed the description of the sociodemographic, sexual, and reproductive aspects associated with a greater likelihood of persistent HPV infection and the development of low-grade (LSIL) and high-grade (HSIL) squamous intraepithelial lesions and cervical cancer in the same population.A higher frequency of patients without lesions or with LSIL than with HSIL or cervical cancer was expected in the infected group, when we considered the probability of the progression of HPV lesions . HoweverThe characteristics that were significantly associated with a higher frequency of HPV infection and the development of intraepithelial lesions in the studied group were age, smoking, monthly income, contraceptives use, preservatives use, age of first sexual intercourse, and educational stage.Age is a characteristic of susceptibility to HPV infection and lesion development that has been well-established in previous studies. Women younger than 24 years or older than 55 years are more affected by infection, as shown in this study ,27,28,29We have shown here that smoking is related to cancer development and HPV infection, confirming previous studies by our group ,29,34. TRegarding contraceptives use, we found a significant association with HPV infection and cervical cancer development, which may be due to endometrial hyperplasia caused by hormonal imbalance, as noted in a recent meta-analysis .The use of preservatives reduces transmission and favors viral elimination . We hypoThe association between ethnicity and susceptibility to HPV infection is complex, especially since the data were obtained based on patient self-report. The Brazilian population is highly admixed, with heterogeneous ancestry that includes both indigenous people and immigrants from Europe, Africa, and Asia . MoreoveCX sequences, where the underlined base is the mutated base, and X can be any base) [The overexpression or variation of APOBEC3 genes has been cited as a possible source of aberrant DNA editing during replication, repair, or transcription, which is capable of inducing somatic mutations that cause genomic instability in cancer cells . Data frny base)  attributny base) ,42.The A3A/B polymorphism confers a greater susceptibility to cancer by generating a hybrid transcript between A3A and A3B 3′UTR that is more stable and more highly expressed in cells . A3A sigIn cervical cancer, there is a microenvironment that favors the mutagenic activity of A3A: 1. The accumulation of A3A is stimulated by the production of interferons in response to viral infection ; 2. the In our study, we found no association of A3A/B polymorphism with infection, LSIL, HSIL, or cervical cancer, which is consistent with previous studies that failed to detect this association in other sample groups ; howeverThe absence of the association of the variant allele with cancer found in our study reflects the population in southern Brazil. This result is consistent with a previous breast cancer study conducted with an independent sample from the same geographic region . The freNevertheless, there is no consensus in the literature on the role of A3A and A3B in the development of lesions and cervical cancer , highligRegarding the study limitations, sampling by convenience may have an influence on the homogeneity of the sample characteristics, mainly the sociodemographic variables. Moreover, the experiment design does not include longitudinal monitoring of the infection and lesion development in the participants, which means that a causal relation of the statistically significant variables is not possible to be assumed. Finally, the specific detection of high- and low-risk infection could be helpful to better characterize the frequency and association of the polymorphism between the groups with lesions or cancer in this population. Despite the limitations that cannot be ignored, the importance of this work is given by the discussion of a genetic variation that is so rarely studied in the different branches of research. The non-association found does not invalidate the valuable discussion about a group of genes intrinsically related to the antiviral response and provides support for future basic research.In this study, we examined the main sociodemographic characteristics and sexual and reproductive behaviors associated with HPV infection and the development of precursor lesions and cervical cancer. We showed that the APOBEC3A/B polymorphism does not contribute to HPV infection or to the development of low- or high-grade cervical intraepithelial lesions and cervical cancer in a southern Brazilian population. Finally, we would like to emphasize that more studies with ethnically different populations must be developed, in order to overcome the limitations described here and validate the non-association of this polymorphism with HPV infection and the resulting lesions.


In Morocco, cervical cancer represents a major public health problem. It ranks second, after breast cancer in Moroccan women, in terms of incidence and mortality. Each year, more than 3,300 new cases and nearly 2,500 deaths are recorded. A Moroccan national program to fight against cervical cancer (CC) based on the practice of visual inspection after application of acetic acid was set up in 2010, allowing screening and possibly of immediate treatment of premalignant lesions of the cervix. In September 2022, a partnership circular between the Ministry of Health and Social Protection (MSPS) and the Ministry of National Education, Preschool and Sports was launched. it announces that the MSPS will integrate the HPV vaccine using the quadrivalent vaccine into the Moroccan National Immune Program (PNI), the vaccination will be aimed to 11-year-old girls, mainly those in school, who will receive two doses separated by at least a period of 6 months. The cervical cancer screening program in Morocco has been institutionalised since 2012. The screening test uses the VIA test for women who is 30-49 years old. It is intended in the National Cancer Prevention and Control Plan framework 2020-2029 to switch to HPV testing for women who is 30 and 40 years old, according to the application of the WHO recommendations which advocate the need to switch to a more efficient screening test [The vaccination using the quadrivalent vaccine has joined the arsenal to eradicate cervical cancer given its effectiveness. Indeed, a literature review of studies measuring the burden of HPV-associated disease and infection in Australia before and after the introduction of HPV vaccine showed that vaccination with the quadrivalent vaccine had a significant impact on HPV-related disease. Of nearly 1,544 HPV-associated cancers in 2012, 1,242 were prevented by the quadrivalent vaccine and a further 187 ano genital cancers could have been prevented by the nanovalent vaccine . GloballIn 2020, the recent estimate of cervical cancer incidence and mortality according to the Global Cancer Observatory indicate that there are approximately 2,165 new cases  . AccordiThe vaccine against HPV infections has been introduced in many countries around the world since 2006/2007, although coverage until now is variable, depending on geographical area and human development index. In 2020, WHO reports that less than a quarter of low-income countries have introduced the HPV vaccine into their national immunisation schedule, while more than 85% of high-income countries have done so . The perThe Kingdom of Morocco has quite respectful experience in eliminating diseases that cause serious public health problems, such as malaria, blinding trachoma, schistosomiasis, leprosy, and certain vaccine-targeted diseases such as diphtheria, neonatal tetanus, and poliomyelitis. It has therefore the ability to meet the challenge of eliminating cervical cancer. Indeed, in September 2022 a directive circular signed by the Health and Social Protection Ministry and the National Education, Pre-school and Sports Ministry, was launched announcing that an HPV vaccine will be integrated in the Moroccan National Immunisation Programme (PNI), using the quadrivalent one. The vaccination will be aimed at schooled girls aged 11 years, mainly those in school, who will receive 2 doses separated by at least 6 months [To conclude, the fight against cervical cancer in Morocco, initially based on visual inspection with acetic acid while waiting to switch to screening by HPV genomic test as suggested by the WHO. The treatment of cervical precancerous lesions basically by the thermo coagulation and alternately by loop electro excision procedure (LEEP), or even by surgery conisation with scalpel blade, is currently completed by the anti HPV vaccination, using the quadrivalent vaccine. In addition, countries with more than 70% vaccination coverage are those that have organised screening. Conversely, countries that have organised neither screening, nor vaccination have a vaccination coverage rates below 50%.


Herein, by employing an InZrOx-Beta composite catalyst in the CO2 hydrogenation, a high selectivity of 53.4% to butane is achieved in hydrocarbons (CO free) under 315 °C and 3.0 MPa, at a CO2 conversion of 20.4%. Various characterizations and DFT calculation reveal that the generation of methanol-related intermediates by CO2 hydrogenation is closely related to the surface oxygen vacancies of InZrOx, which can be tuned through modulating the preparation methods. In contrast, the three-dimensional 12-ring channels of H-Beta conduces to forming higher methylbenzenes and methylnaphthalenes containing isopropyl side-chain, which favors the transformation of methanol-related intermediates to butane through alkyl side-chain elimination and subsequent methylation and hydrogenation. Moreover, the catalytic stability of InZrOx-Beta in the CO2 hydrogenation is considerably improved by a surface silica protection strategy which can effectively inhibit the indium migration.Direct conversion of CO 2 to a specific hydrocarbon with high selectivity is attractive but challenging. Here the authors report a highly active InZrOx-Beta tandem catalyst for CO2 hydrogenation to butane and develop a surface silica protection strategy to inhibit the migration of indium species, greatly improving catalytic stability.Direct conversion of CO In this regard, the conversion of CO2 into bulk chemicals including light olefins12 and aromatics16 has attracted special attention. Two routes are now proposed for the CO2 hydrogenation, viz., the modified Fischer-Tropsch synthesis (FTS) one using Fe- or Co-based catalysts21 and the methanol-mediated one over a composite catalyst consisting of metal oxides and zeotypes (OX-ZEO)22. As the FTS route keeps to the Anderson-Schultz-Flory (ASF) rule for the product distribution, a wide spectrum of hydrocarbons are produced. In contrast, the selectivity to the target olefin and aromatic products can be considerably improved by using the OX-ZEO composite catalyst via the methanol-mediated route which dispenses with the ASF rule23.The hydrogenation of CO2 to C2–C3 alkenes/alkanes in recent years. Through the regulation of surface electronic structure of metal oxides and acidic properties of zeotypes, a high selectivity to ethene (ca. 70%)24, propene + butene (ca. 65%)25, or propane (ca. 70%)26 was achieved for the CO2 hydrogenation. Nonetheless, it is very challenging to achieve a high selectivity to a defined hydrocarbon (in particular a relatively long chain one) through the CO2 hydrogenation, due to the chemical inertia of CO2 and the complexity of C–C coupling reactions. For example, the selective hydrogenation of CO2 into C4+ hydrocarbons is rarely reported27, although the C4+ hydrocarbons are highly valuable as clean fuel and solvents. In this regard, butane is widely used as fuel (liquefied gas), refrigerant, spray, and feedstock in chemical synthesis. Traditionally, butane is obtained from petroleum cracking28. The direct conversion of CO2 to butane under mild reaction conditions may provide a new strategy for the renewable production of C4+ chemicals. Unfortunately, current reported catalyst in general gave a rather low selectivity to butane (<30%)29. In addition, to improve the practicability of CO2 hydrogenation to demanded hydrocarbons, the formation of CH4 (from CO2 methanation) and CO  should also be suppressed to the utmost.Great progress has been made in the hydrogenation of CO2 hydrogenation over a bifunctional OX-ZEO catalyst, first, the oxide moiety should be highly effective in building methanol-related intermediate. In2O3 is a promising catalyst component for the CO2 hydrogenation to methanol, showing high activity at a high temperature of 280–330 °C32. To suppress the formation of CH4 and CO, various dopants were used to regulate the crystal structure and surface electronic properties of In2O336; among them, doping Zr into In2O3 proved to be rather effective. Frei and co-workers observed that Zr was able to increase the concentration of surface oxygen vacancies of In2O3, which could then promote the adsorption and activation of CO2 and raise the selectivity to methanol37. Chen and co-workers found that the interfacial interaction between In2O3 and ZrO2 was favorable to the formation of methanol38. Similarly, a high methanol space time yield (STY) was observed over InZrOx in the CO2 hydrogenation40.For the CO42. Naturally, the distribution of products on the OX-ZEO catalysts is closely related to the topology framework and acidity of the zeotype moiety. Various composite catalysts like InZrOx/SSZ-1326, In2O3/SAPO-3435, and In2O3/ZSM-543 were used in the CO2 hydrogenation, which were selective to alkanes (C20–C40), light olefins (C2=–C4=), and liquid fuels, respectively. It implies that higher alkanes/alkenes like butane may request the zeotype moiety a relative large pore channel such as Beta, which can accommodate large reaction intermediates and allow the quick diffusion of large molecular products. In addition, the facile synthesis of Beta zeolite with a wide range of Si/Al ratio makes it attractive as a catalyst component in the conversion of methanol44. It is then expected that a bifunctional catalyst composed of Zr-doped In2O3 and H-Beta may give a high yield of C4 hydrocarbons for the CO2 hydrogenation. However, we have seldom noticed such reports in this regard, despite that the In-based catalysts have been widely used in the CO2 hydrogenation to alcohols and light alkene and alkane mixtures. In addition, Wang and co-workers reported recently that the indium species in the oxide moiety would continuously run off during the reaction process, resulting in a rapid poisoning of the acid sites on the zeotype moiety45, which may also inhibit the application of In2O3 in the bifunctional catalyst in practice for the CO2 hydrogenation to hydrocarbons.Next, the zeotype moiety must work in close cooperation with the oxide moiety to achieve a high yield of specific hydrocarbon. The zeotype moiety is responsible for the successive transformation of the methanol-related intermediates generated on the oxide moiety into hydrocarbons on the acid sites in the confined interspacex oxide and H-Beta zeolite was designed and employed in the hydrogenation of CO2; a high selectivity of 53.4% to butane in all hydrocarbons (CO free) is achieved under 315 °C, 3.0 MPa, and a space velocity of 1200 mL g−1 h−1 (H2/CO2 = 3), at a CO2 conversion of 20.4% and a selectivity of only about 2% to CH4. Combining with various characterization measures and density-functional theory (DFT) calculation, it is revealed that the high selectivity to butane originates from the hydrocarbon pool (HCP) in the H-Beta zeolite filled with bulkier methylbenzenes and methylnaphthalenes, via an alkyl side-chain intermediate. Moreover, a surface silica protection strategy was developed, which can effectively inhibit the phase separation of InZrOx oxide and the migration of In species into the H-Beta zeolite and then considerably improve the catalytic stability of InZrOx-Beta in the CO2 hydrogenation. These results pave a way for the design of stable In-based catalyst in the CO2 hydrogenation to a specific hydrocarbon product.Herein, a bifunctional composite catalyst consisting of InZrOx oxides prepared by different methods determined by N2 sorption. Apparently, the surface area of three InZrOx oxides decreases in the order of InZrOx(CP) (73 m2 g−1) > InZrOx(SG) (59 m2 g−1) > InZrOx(HT) (41 m2 g−1); in addition, InZrOx(CP) also displays much larger mesopore volume (0.31 cm3 g−1) than InZrOx(SG) (0.07 cm3 g−1) and InZrOx(HT) (0.15 cm3 g−1).Supplementary Table x oxides prepared by different methods. In the HRTEM images, the (211) and (222) crystal facets, with a lattice spacing of 0.405–0.410 and 0.290–0.291 nm, respectively, are resolved for three InZrOx oxides 42. Furthermore, the TEM images shown in Supplementary Fig. x oxides are aggregates of spherical nano particles (NPs), with a mean size of 9.76 nm for InZrOx(CP) (prepared by co-precipitation), 9.19 nm for InZrOx(SG) (by sol-gel method), and 25.18 nm for InZrOx(HT) . The STEM-EDX elemental mapping results indicate that the In, Zr, and O elements are uniformly dispersed with each other in the InZrOx oxides , oxygen around the vacancies (Odefect), and lattice oxygen (Olattice), respectively. The deconvolution results indicate that the fraction of surface oxygen around the vacancies (representing the abundance of oxygen vacancies) for three InZrOx oxides decreases in the order of InZrOx(CP) (36.15%) > InZrOx(SG) (32.39%) > InZrOx(HT) (27.65%). In addition, the same sequence of three oxides by the surface oxygen vacancy concentration is manifested by the in situ O 1s XPS results  (43.47%) > InZrOx(SG) (36.75%) > InZrOx(HT) (31.76%). The in situ O 1s XPS gives higher surface oxygen vacancy concentrations than the ex situ one, which is ascribed to the fact that more surface oxygen defects are formed due to the elimination of certain surface oxygen atoms by reduction in the in situ H2-containing atmosphere, in agreement with previous works47.The surface electronic state of various InZrOdes Fig. 46; the p2-TPR profiles of various InZrOx oxides. The high temperature peak (centered around 650 °C) is attributed to the reduction of bulk In2O3, whereas the low temperature one (150–250 °C) is due to the annihilation of surface oxygen from In2O347. Apparently, InZrOx(CP) displays a more intense H2 consumption peak (19 μmol g−1) attributed to the removal of surface oxygen at a lower temperature (160 °C), in comparison with InZrOx(SG)  and InZrOx(HT) , indicating that InZrOx(CP) has more surface defects (oxygen vacancies), agreeing well with above O 1s XPS results. The Rietveld refinement of the in situ XRD patterns  also displays the highest cell shrinkage ratio than InZrOx(SG) and InZrOx(HT), according well with the more surface defects of InZrOx(CP). Moreover, since the onset temperature for the reduction of bulk In2O3 to metallic indium species is only around 315 °C, it is conceivable that certain metallic indium species may be generated on the surface of InZrOx oxide during the reduction and subsequent reaction processes. These metallic indium species may easily migrate to the zeolite moiety and then poison the acid sites of zeolite component47; this will be discussed in detail in the following section.Figure 2-TPD profiles of various InZrOx oxides. The peak below 150 °C represents the physical adsorption of CO2, whereas that at above 300 °C is ascribed to the chemical adsorption of CO2 on the surface oxygen defects42. As expected, InZrOx(CP) exhibits larger CO2 desorption amount at above 300 °C, followed by InZrOx(SG) and InZrOx(HT). It further evinces that CO2 adsorption is enhanced on InZrOx(CP) (prepared by co-precipitation) with abundant oxygen vacancies.Figure 2 sorption results  of 2400 mL g−1 h−1 and H2/CO2 ratio of 3 in the feed. As shown in Supplementary Fig. x(CP) prepared by co-precipitation exhibits a higher CO2 conversion (18.7%) and a higher methanol space time yield (STY) (0.012 mol kg−1 h−1) than InZrOx(SG) prepared by sol-gel method  and InZrOx(HT) by hydrothermal method .The InZrOx-Beta catalyst (0.3 g InZrOx + 0.3 g H-Beta) was evaluated in the hydrogenation of CO2 under 315 °C, 3.0 MPa, a SV of 1200 mL g−1 h−1, and an H2/CO2 ratio of 3 in the feed. As shown in Fig. x-Beta(40), butane is the dominant hydrocarbon product. In particular, InZrOx(CP)-Beta(40) exhibits a selectivity of 53.4% to butane in the hydrocarbon products, at a CO2 conversion of 20.4% and a selectivity of 54.9% to CO. In contrast, over InZrOx(SG)-Beta(40), the selectivity to butane in the hydrocarbon products, CO2 conversion, and selectivity to CO are 52.9%, 18.7%, and 53.0%, respectively, whereas over InZrOx(HT)-Beta(40), the CO2 conversion decreases to 12.6%, whilst the selectivity to butane decreases to 34.7%, accompanied by the formation of more C2–C3 components. It seems that InZrOx(CP) with abundant oxygen vacancies exhibits high activity in the CO2 hydrogenation to methanol; when composed with H-Beta(40), the InZrOx(CP)-Beta(40) composite catalyst also displays excellent performance in the tandem transformation of CO2 to butane.Next, the catalytic performance of granule-mixed bifunctional InZrO2 hydrogenation are also closely related to the topology framework and acidic properties of the zeotype moiety in the bifunctional composite catalyst. As shown in Fig. x(CP)-Beta, whereas more C2–C3 and C5+ hydrocarbons are generated over InZrOx(CP)-SSZ-13 and InZrOx(CP)-USY with smaller windows and larger cavities. It indicates that the 3D 12-ring channels of H-Beta is pertinent for the transformation of methanol-related intermediates (generated from CO2 hydrogenation over the oxide moiety) into butane.Besides the oxide moiety, the yield and spectrum of hydrocarbon products for the CO2 hydrogenation over InZrOx(CP)-Beta is associated with the acid density of the H-Beta zeolite moiety. As shown in Fig. 2–C3 components decreases, whereas the fraction of C5+ components in the product increases, whilst the selectivity to C4 hydrocarbons (dominated by butane) achieves the maximum value at a Si/Al ratio of 40. A higher Si/Al ratio  may weaken the capability of alkenes hydrogenation and then yield more alkenes. In particular, InZrOx(CP)-Beta(100) displays even an incomplete conversion of methanol due to its rather low acid density. In contrast, excessive acid sites in H-Beta zeolite (e.g. Beta(20), with a very low Si/Al ratio) conduce to the cracking of long-chain hydrocarbons and then generate more small alkenes/alkanes48. Therefore, the selectivity to butane shows a volcanic curve with the Si/Al ratio of H-Beta and gets to the maximum value of 53.4% over InZrOx(CP)-Beta(40). Notably, isobutane accounts for 86.5% of two butane isomers.Moreover, the product distribution for the CO2, which acts also vividly in the competitive reverse water-gas (RWGS) reaction6, the possible role of water in the reaction process was further evaluated by adding different proportions of water into the H2 and CO2 feed. As shown in Supplementary Fig. 2 conversion decreases from 19.1 to 8.9%, along with the attenuation of the selectivity to CO from 54.7 to 34.0%. Such a phenomenon becomes more evident when the proportion of water in the feed increases from 7.5 to 15.1% , leading to the decline of the CO2 conversion and the selectivity to CO9. In addition, water molecules may also compete for the active adsorption sites with the reactants, which may also abate the conversion of CO2 to hydrocarbons.As water is a co-product in the hydrogenation of CO2 and selectivity to CO are both spontaneously rejuvenated, when the co-feeding water is cut off -Beta(40). As shown in Fig. 2 conversion increases from 11.4% to 28.8%, despite that more CO are produced due to the promotion of the reverse water-gas shift (RWGS) reaction at a higher temperature6. Meanwhile, the selectivity to butane and C5+ decreases gradually with the increase of temperature, accompanied by the formation of more C1–C3 products due to the aggravated cracking of long-chain hydrocarbons, as also observed by Ding and co-workers49.The reaction temperature has a great influence on the product yield and spectrum for the hydrogenation of CO2 conversion from 16.6 to 20.4%, but decreases the selectivity to CO from 65.4 to 54.9%, as shown in Fig. 1–C3 alkanes, at the expense of butane and C5+ hydrocarbons.In contrast, an increase of the reaction pressure from 0.1 to 3.0 MPa (at 315 °C) elevates the COx(CP)-Beta(40) composite on the CO2 hydrogenation was also considered, as demonstrated in Fig. 2 conversion and selectivity to CO decrease from 21.7% and 57.5% to 18.5% and 49.6%, respectively, while the highest selectivity to butane (53.4%) is achieved at an oxide/zeolite mass ratio of 1.The effect of the oxide/zeolite mass ratio in the InZrO2/CO2 ratio in the feed also have certain influence on the CO2 hydrogenation. A decrease of the space velocity from 2400 to 800 mL g−1 h−1 makes the CO2 conversion increase from 14.9 to 23.4%, despite that the formation of CO is also promoted  and H-Beta(40) from dual-bed filling to granule stacking makes the CO2 conversion and selectivity to butane slightly increase from 19.1% and 53.1% to 20.4% and 53.4%, respectively. However, the composite catalyst prepared by powder mixing of the two moieties just produces large amounts of methane (40.2%) and methanol (24.2%), due to the rapid deactivation of H-Beta zeolite. Similar phenomenon was also observed by Wang and co-workers45; that is, the In species may easily migrate from the metal oxide moiety to the zeotype moiety when the two moieties are in very close contact, resulting in the rapid passivation of the acid sites in the zeotype moiety that are responsible for the successive transformation of methanol-related intermediates to hydrocarbons.In addition, the manner used to compose the InZrOx(CP)-Beta(40) composite catalyst composed by granule stacking with equal mass of oxide and zeolite exhibits excellent performance in the selective hydrogenation of CO2 to butane. Under 315 °C, 3.0 MPa, a space velocity of 1200 mL g−1 h−1, and an H2/CO2 ratio of 3 in the feed, a high selectivity of 53.4% to butane in all hydrocarbons is achieved, at a CO2 conversion of 20.4% and a selectivity of only about 2% to CH4.On all accounts, the bifunctional InZrO2 hydrogenation to methanol over the InZrOx(CP), InZrOx(SG), and InZrOx(HT) oxides, as shown in Fig. 2 and CO2 for reaction over InZrOx(CP) for 1 min, the vibration bands attributed to the carbonate (CO32−/HCO3−) species appear at 1506, 1650, and 1700 cm−1 52, belonging to the signals of activated CO2  species are simultaneously detected54. With the proceeding of the reaction process, the peak intensity of HCOO* and H3CO* species decreases gradually, as they are hydrogenated to methanol. Such phenomena confirm that formate and methoxy are crucial intermediates for methanol formation in the CO2 hydrogenation over InZrOx(CP), in line with the previous reports53. In comparison with InZrOx(CP), InZrOx(SG) and InZrOx(HT) also show the characteristic peaks of the formate and methoxy species, but in a much lower intensity  in the H2 atmosphere over the H-Beta(40) zeolite. As shown in Fig. 2 hydrogenation over InZrOx-Beta(40) (53.4%).The methanol-related intermediates generated on the InZrO55. As demonstrated in Fig. 57. After the elimination of isopropyl side-chain, the generated propene can be further converted to butane through methylation and subsequent hydrogenation reactions. In fact, certain polyMBs and polymethylnaphthalenes (polyMNs) with isopropyl side-chain  and 8-isopropyl-2,5-dimethyl-1,2,3,4-tetrahydronaphthalene (isopropyl-MN)) are simultaneously detected by GC-MS , according well with their high activity in MTH -Beta(40) catalyst after the CO2 hydrogenation test, as shown in Supplementary Fig. x(HT)-Beta(40) catalyst is rather lower than that on the spent InZrOx(CP)-Beta(40) catalyst  in the CO2 hydrogenation to methanol; that is, as less methanol-related intermediates are formed on the InZrOx(HT) moiety with poorer activity in the CO2 hydrogenation, the formation and growth of higher polyMBs as the HCP species for MTH are also greatly restricted in the H-Beta moiety, leading to the lower yield of butane over the InZrOx(HT)-Beta composite catalyst , whereas the H-Beta moiety is accountable to the subsequent transformation of methanol-related intermediates into hydrocarbons (similar to methanol to hydrocarbons (MTH), via the hydrocarbon pool mechanism). As a result, the conversion of CO2 is mainly related to the InZrOx moiety; InZrOx(CP) prepared by co-precipitation has abundant oxygen vacancies and great capacity for the CO2 hydrogenation to methanol. In contrast, the product distribution is mainly associated with the framework topology and acidity properties of the zeotype moiety. The H-Beta zeolite of 3D 12-ring channels with moderate acidity (Si/Al = 40) is appropriate for the construction of HCP containing abundant higher polyMBs and polyMNs as well as the production of butane via the aromatic-based cycle of HCP mechanism through the isopropyl side-chain elimination and subsequent methylation and hydrogenation reactions. In addition, the granule-mixing manner used to compose the InZrOx-Beta bifunctional catalyst can realize a pertinent contact between two moieties and then achieve a prominent coupling of two reaction steps .On all accounts, the CO2 to hydrocarbons59. The degeneration of metal oxide often causes a rapid decrease in the CO2 conversion, as the adsorption and activation of CO2 are mainly performed on the surface of metal oxide43. As for the acidic zeolite, it catalyzes the subsequent transformation of the methanol-related intermediates previously generated on the oxide moiety into hydrocarbons; the rapid increase in the selectivity to unconverted methanol is an important sign for the deactivation of the zeolite component61. For the In-based bifunctional catalyst, the indium species may facilely migrate from the oxide moiety into the zeotype moiety in the H2-containing atmosphere, which can passivate the acid sites in the zeotype moiety and then rapidly deactivate the whole composite catalyst used in the CO2 hydrogenation by lowering capacity of the acidic zeolite component in the transformation of methanol-related intermediates to hydrocarbons45.The degeneration of either the metal oxide moiety or the zeotype moiety can deactivate the whole bifunctional OX-ZEO catalyst system in the hydrogenation of CO2 hydrogenation over InZrOx(CP)-Beta(40) after reaction for 42 h on stream; thereafter, the selectivity to methanol and DME increases quickly, accompanied by a considerable decrease of the selectivity to butane, suggesting the rapid degeneration of the Beta zeolite. Meanwhile, more CO is generated, due to the shrinking of the methanol conversion capacity of the H-Beta zeolite that may relatively promote the competitive RWGS reaction5. After the reaction test, certain amounts of the In element are detected in the H-Beta moiety (Supplementary Table x(CP) during the CO2 hydrogenation reaction. In fact, the migration of indium species turns to be a fatal defect for the application of the In-based bifunctional catalyst in practice for the hydrogenation of CO2 to hydrocarbons; it is pressing but also rather challenging to effectively inhibit the migration of the In species.As shown in Fig. (CP)-Beta0 after r2 hydrogenation, a surface silica protection strategy was adopted in current work; that is, certain amount of SiO2 (4 wt.% for InZrOx(SCP-4) and 8 wt.% for InZrOx(SCP-8)) was deposited on the InZrOx(CP) oxide through impregnation with tetraethylorthosilicate (TEOS) solution and subsequent calcination at 500 °C . In addition, no diffraction peaks of SiO2 are detected, suggesting that SiO2 is highly dispersed on the InZrOx surface and/or present in amorphous phase. The EDX elemental mapping results show that the silica species are evenly distributed on the surface of InZrOx(CP), despite that they cannot be clearly distinguished by XRD, HR-TEM and Aberration-corrected HAADF-STEM  and InZrOx(SCP-8) oxides also show larger surface area than InZrOx(CP), as revealed by the N2 sorption results  and InZrOx(SCP-8) oxides have the average particle size of 6.10 and 4.70 nm, respectively, much smaller than that of the unmodified InZrOx (9.76 nm)  and InZrOx(SCP-8) shift towards higher binding energies, whereas the Si 2p signal moves to lower value, compared to the corresponding signals of the unmodified InZrOx(CP) counterpart. This is indicative of a strong interaction between the InZrOx(CP) and silica species, which is confirmed by the H2-TPR results; the reduction of both defect In2O3 sites and bulk In2O3 in InZrOx(SCP-4) and InZrOx(SCP-8) requires higher temperature than that in the unmodified InZrOx(CP) counterpart  and charge difference density (CDD) results. As shown in Supplementary Fig. x oxide in the CDD plot, substantiating an intense interaction of the Si 2p orbitals with the In 3d orbitals around Fermi level. Such strong interaction makes the reduction and migration of indium species in the silica-modified InZrOx(SCP-4) and InZrOx(SCP-8) oxides more difficult than that in the unmodified InZrOx(CP) counterpart.Moreover, the XPS spectra shown in Fig. art Fig. . The strx-Beta composite by the surface silica protection strategy. For the un-protected InZrOx oxide, indium species may be easily reduced to metallic In species in the reductive atmosphere, which facilely migrate to the H-Beta component and then passivate the acid sites, leading to the rapid deactivation of the composite catalyst. In contrast, after the surface silica modification, the strong interaction between the SiO2 and InZrOx species can suppress the reduction of In2O3 to metallic indium species and then effectively hinder the metallic indium species from migration into the H-Beta component. Consequently, the structural and catalytic stability of the InZrOx-Beta composite during the reduction and CO2 hydrogenation processes can be greatly improved by the surface silica protection strategy.A schematic diagram is then plotted in Supplementary Fig. x(SCP-4)-Beta(40) and InZrOx(SCP-8)-Beta(40) in the CO2 hydrogenation was then compared with that of the InZrOx(CP)-Beta(40) counterpart. As shown in Fig. x(CP)-Beta(40) to 97 h of InZrOx(SCP-4)-Beta(40) under the same conditions, indicating the higher catalytic stability of latter InZrOx(SCP-4)-Beta(40). Meanwhile, the acidic properties of the H-Beta zeolite component separated from various spent InZrOx-Beta composite catalysts after reaction for the same time were evaluated, as demonstrated in Supplementary Fig. x(SCP-4)-Beta(40) catalyst are both much higher than that separated from the InZrOx(CP)-Beta(40) counterpart. This further confirms that the surface silica protection strategy to alleviate the rapid passivation of the acid sites in H-Beta is rather effective in improving the stability of the bifunctional InZrOx-Beta composite catalyst in the CO2 hydrogenation to hydrocarbons.The catalytic performance of InZrOx(SCP-4)-Beta(40) is reduced to 34.5% from the value of 51.2% over InZrOx(CP)-Beta(40), being much lower than those reported for the In-based bifunctional catalysts in the CO2 hydrogenation in the literature at a similar CO2 conversion  of InZrOx(SCP-8)-Beta(40) is further prolonged to above 140 h, along with a lower selectivity to CO (33.1%), as shown in Fig. In addition, the selectivity to CO over InZrO2-modified and unmodified InZrOx-Beta catalysts during the steady stage, the selectivity to butane for the CO2 hydrogenation over the InZrOx(SCP-4)-Beta(40) and InZrOx(SCP-8)-Beta(40) composite catalysts still decreases gradually after a long time on stream (ca. 70–100 h). It indicates that the surface silica modification method may not completely and eternally solve the problem of indium species migration. Nevertheless, the onset time for the decrease in the selectivity to butane is extended from 40 h of InZrOx(CP)-Beta(40) to ca. 70 h of InZrOx(SCP-4)-Beta(40) and ca. 100 h of InZrOx(SCP-8)-Beta(40), as demonstrated in Supplementary Fig. 2 loading is favorable for lowering the impact of indium migration on the butane formation. However, the deposited SiO2 may also cover a fraction of the surface oxygen vacancies, which leads to a decrease of CO2 adsorption capacity on the SiO2-modified InZrOx oxides  and InZrOx(SCP-8) have a lower concentration of surface oxygen vacancies but abundant OH groups originated from the surface Si–OH of SiO2, in comparison with the InZrOx(CP) counterpart. Consequently, the CO2 conversion is also decreased from 25.6% over InZrOx(CP)-Beta(40) to 19.7% over InZrOx(SCP-4)-Beta(40), and further to 16.6% over InZrOx(SCP-8)-Beta(40). Accordingly, the loading of SiO2 for the surface protection of the InZrOx oxide should be restricted to a certain value (ca. 4–8 wt.%) to elevate the catalytic stability of catalyst and meanwhile avoid a substantial decrease of the CO2 conversion.Notably, although the selectivity to butane keeps at around 53% over both the SiOx(CP) oxide and H-Beta zeolite in the InZrOx(CP)-Beta composite were separated from each other and then characterized by various measures. According to the TG analysis results , indicating that the coke deposition here should not be the major cause of catalyst deactivation. Unlike the conversion of methanol to hydrocarbons (MTH) over a zeolite catalyst in the N2 or Ar atmosphere, for the hydrogenation of CO2 to hydrocarbons, the presence of H2 and H2O in high pressure can effectively eliminate the coke precursors and thus greatly hinder the formation and accumulation of coke species. However, in the XRD patterns shown in Fig. 2O3 is distinctly detected on the H-Beta zeolite separated from the spent InZrOx(CP)-Beta(40) catalyst, which is further verified by the identification of InZrOx nano-particles in the TEM image on the surface of separated H-Beta zeolite -Beta and InZrOx(SCP-8)-Beta catalysts  and InZrOx(SCP-8) oxides during the CO2 hydrogenation reaction.After the reaction test, the granules of InZrOite Fig. . In contsts Fig. , suggestx(SCP-4) and 140 h over InZrOx(SCP-8), the diffraction peaks in the XRD patterns and the binding energies in the In 3d, Zr 3d and Si 2p XPS spectra of the spent InZrOx(SCP-4) and InZrOx(SCP-8) oxides are highly comparable to those of the corresponding fresh ones  and InZrOx(SCP-8) oxides  and InZrOx(SCP-8) samples have a particle size of 7.57 and 5.16 nm, respectively, only slightly larger than the values of 6.10 and 4.70 nm for the fresh InZrOx(SCP-4) and InZrOx(SCP-8) counterparts, respectively -Beta(40) catalyst shows a long catalytic lifetime (ca. 65 h) and high selectivity to butane (ca. 53% in hydrocarbons) in the CO2 hydrogenation. In contrast, over the unmodified In2O3(CP)-Beta(40) counterpart, the selectivity to butane is quickly decreased to 30%, along with the generation of much more unconverted methanol (25%) after reaction for ca. 65 h -Beta(40) catalyst also originates from the inhibition of the indium species from reduction and migration by the surface silica protection, which can alleviate the rapid deactivation of the zeolite moiety in the hydrogenation of CO2 to hydrocarbons  after reaction for different periods of time are analyzed. Apparently, the diffraction peaks in the XRD patterns, the lattice spacing in the HRTEM images and the binding energies in the In 3d, Zr 3d and Si 2p XPS spectra of the spent InZrOx(SCP-4)-24h and InZrOx(SCP-4)-42h samples are all highly comparable to those of the fresh counterpart  is only slightly increased from 6.10 nm of fresh InZrOx(SCP-4) to 6.89 nm of InZrOx(SCP-4)-24h and to 7.30 nm of InZrOx(SCP-4)-42h  also show little change upon the CO2 hydrogenation reaction test  is achieved at a CO2 conversion of 20.4% and a selectivity of only about 2% to CH4.A composite bifunctional catalyst consisting of InZrO2 to butane keeps to the tandem methanol-mediated mechanism and the catalytic performance of the InZrOx-Beta composite is related to both the InZrOx oxide moiety and the H-Beta zeolite moiety. The generation of methanol-related intermediates by CO2 hydrogenation is closely related to the surface oxygen vacancies of InZrOx, which can be finely tuned through modulating the preparation methods. In contrast, the three-dimensional 12-ring channels of H-Beta zeolite conduces to forming a hydrocarbon pool (HCP) filled with higher methylbenzenes and methylnaphthalenes, which favors the successive transformation of methanol-related intermediates to butane via the aromatic-based cycle, through the alkyl side-chain elimination and subsequent methylation and hydrogenation.Various characterization measures and DFT calculation were used to explore the reaction mechanism and structure-performance relationship. The results reveal that the conversion of COx in the reductive atmosphere containing H2, a surface silica protection strategy was developed, which can effectively inhibit the phase separation of InZrOx oxide and the indium migration, and then considerably improve the catalytic stability of InZrOx/Beta in the hydrogenation of CO2 to hydrocarbons. The insight shown in this work may pave a way for the design of stable In-based catalyst in the CO2 hydrogenation to get a specific hydrocarbon product.In addition, to tackle the passivation of the acid sites in H-Beta by the migration of indium species of InZrOx oxides with an In/Zr molar ratio of 4 were prepared, viz., InZrOx(CP) by co-precipitation, InZrOx(SG) by sol-gel processing, and InZrOx(HT) by hydrothermal method. In addition, InZrOx(CP) was further modified by depositing 4 and 8 wt.% SiO2 on the surface, to obtain the SiO2-modified InZrOx(SCP-4) and InZrOx(SCP-8) oxides, respectively. Meanwhile, a series of H-Beta zeolites with a Si/Al molar ratio (n) of 20, 30, 40, 60, and 100 were synthesized by the hydrothermal method and denoted as Beta(n). Moreover, H-USY (Si/Al = 5.5) and H-SSZ-13 (Si/Al = 9), purchased from Nankai University Catalyst Co., were used for comparison.As described in detail in the Supplementary Information, three InZrOx-Beta bifunctional catalysts, viz., dual-bed, granule-mixing, and powder-grinding. By the dual-bed manner, 0.3 g of granule InZrOx (20–40 mesh) was used as the upper layer and 0.3 g of granule H-Beta (20–40 mesh) as the lower layer. By granule-mixing, 0.3 g of InZrOx and 0.3 g of H-Beta (both in 20–40 mesh) was mixed in granules. By powder-mixing, 0.3 g of powder InZrOx and 0.3 g of powder H-Beta were grinded together for 5 min and the powdery mixture was then granulated into particles of 20–40 mesh.Three manners were used to compose the InZrO2 sorption, X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Aberration-corrected high-angle annular dark-field scanning TEM (Aberration-corrected HAADF-STEM), temperature-programmed reduction with H2 (H2-TPR), temperature-programmed desorption of NH3 (NH3-TPD) and CO2 (CO2-TPD), thermogravimetric analysis (TGA), inductively coupled plasma-atomic emission spectrometer (ICP-AES), in situ diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and 12C/13C methanol switching experiment, as described in detail in the Supplementary Information.Various catalyst samples were characterized by N2 hydrogenation reaction was carried out in a stainless steel tubular fixed-bed reactor, as described in detail in the Supplementary Information. Briefly, for the CO2 hydrogenation to methanol, 0.3 g of InZrOx was used and the reaction was conducted under 315 °C, 3.0 MPa, and with a space velocity (SV) of 2400 mL g−1 h−1 and H2/CO2 ratio of 3 in the feed. For the CO2 hydrogenation to butane, unless specially claimed, 0.6 g of granule-mixed bifunctional InZrOx-Beta catalyst (0.3 g InZrOx + 0.3 g H-Beta) was used and the reaction was performed under 315 °C, 3.0 MPa, a SV of 1200 mL g−1 h−1, and H2/CO2 ratio of 3 in the feed. For the InZrOx(CP)-Beta composite catalyst prepared by granular mixing, two components of InZrOx(CP) and H-Beta in the spent InZrOx(CP)-Beta catalyst after the reaction test were distinctly different in color, as displayed in Supplementary Fig. 2 as the carrier gas, under 315 °C, atmospheric pressure and a methanol weighted hourly space velocity (WHSV) of 0.05 h−1.The CODFT calculation was conducted with the Gaussian 09.E01 package, as described in detail in the Supplementary Information.Supplementary InformationPeer Review File


Investigate HPV types in cervical specimens, their correlation with p16 expression in lesions, and diagnostic value for cervical lesions. Enhance clinical diagnosis reliability.Retrospective cross-sectional study at Fujian Maternity and Child Health Hospital’s Cervical Disease Center (Jun 2019-Dec 2021). Patients with abnormal cervical screening underwent colposcopy and conization. Pathological diagnosis based on colposcopy, cervical biopsy, ECC, and conization. Analyzed HPV genotyping  and p16 expression correlation. Statistical analysis used R software.he expression of p16 is significantly associated with the infection of high-risk HPV types, such as 16, 33, 52, and 58, with an increased risk of 1.4 times or higher . The risk of p16 expression increased 4-fold for multiple high-risk HPV types . Compared to the p16(-) group, the p16(+) group had a higher association with cervical lesions worse than HSIL .In the group with multiple Human Papillomavirus Infections with types 16, 33, 52, and 58, the risk of cervical lesions worse than HSIL increased by up to 660-fold compared to the negative group , indicating that this combination of HPV types posed the greatest risk for cervical lesions above HSIL.p16 plays a crucial role in cervical lesion progression, linked to high-risk HPV. Combining p16 with HPV screening improves cervical cancer detection. Studying multiple HPV infections will enhance prevention and management. At presThe development of cervical cancer is a long-term and continuous process of tumor progression, which includes cytological abnormalities, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and finally, carcinogenesis. This process requires the involvement of multiple pathogenic factors, multiple oncogenes, and occurs through a series of steps , 4. One Currently, HPV-DNA detection is the primary screening method for cervical cancer in China. However, it has its limitations, including high sensitivity and low specificity due to the influence of various factors in both the host and the virus . EspeciaTo improve the accuracy of cervical cancer detection and prognosis, researchers have been investigating the role of p16, a tumor suppressor gene involved in the progression of uterine cervical lesions . The p16However, while the significance of p16 in cervical cancer progression has been studied, there is still a lack of research on its interaction with different HPV infection genotypes . As a reIn this study, we conducted a retrospective analysis of patients with cervical lesions using histopathology as the standard for diagnoses . All pat22.1in situ (AIS), Squamous Cell Carcinoma (SCC), and Adenocarcinoma. The interval between cervical cancer screening and histological examination was less than 3 months. Clinical information, including age, gravidity, parity, HPV genotypes, and cervical pathology, was extracted from the department’s medical records  and/or HPV genotyping. Abnormal cytology results were defined as Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-grade Squamous Intraepithelial Lesion (LSIL), High-grade Squamous Intraepithelial Lesion (HSIL), Atypical Glandular Cells (AGC), Endocervical Adenocarcinoma  records Figure 1The study was conducted in compliance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University (2023KY038). Due to the retrospective nature of the study, informed consent was exempted.2.2PCR-RDB HPV genotyping (Yaneng Biotech) was performed to identify 18 genotypes of high-risk HPV (HR-HPV): HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82, and 83, as well as 5 types of low-risk HPV (LR-HPV): HPV-6, 11, 42, 43, and 81.2.3Colposcopy referrals were based on the ASCCP guidelines . All patThe final pathological diagnosis was determined using the most severe result among evaluations of cervical biopsies, ECC, and conization tissues. The histologic endpoints were defined according to the 2014 WHO classification of tumors of the female reproductive organs (4th Edition)  and Lowe2.4The Leisegang D-10625, Model1DS Ur Nr 55764, Colposcope from Berlin, Germany, was used for cervix examination. After exposing the cervix using an appropriately sized Cusco’s speculum, the vulva, vagina, and cervix were examined before the application of 3% acetic acid solution for each patient. Colposcopic abnormalities were classified as normal, abnormal, or unsatisfactory. Biopsies were taken from abnormal areas using punch cervical biopsy tissue forceps. The cervical specimens were processed in the histopathology laboratory, and a histopathologist blinded to the HPV status of the participants performed the diagnosis. Immunocytochemical staining was performed using the P16/Ki67 double staining kit on each cervical specimens. Experimental operations were strictly in accordance with the kit instructions and the technical instructions for double staining of cervical cells, and two experienced pathologists conducted and interpreted the double staining of cervical epithelial cell.2.5Categorical variables were presented as frequencies (percentages), and statistical analyses were performed using R software and its packages . Descriptive statistics showed mean ± standard deviation for continuous variables, while frequency and percentage were used for categorical variables. The statistical differences among p16 status for clinical characteristics were tested with t-tests for continuous variables and Chi-square tests for categorical variables. Univariate and multivariate logistic regression analyses, adjusting for age, gravidity, parity, and pregnancy, were used to determine the association between multiple HPV infections and cervical lesions. Two-tailed P-values less than 0.05 were considered statistically significant.33.1The analysis included a total of 5165 female patients with definitive pathological diagnoses. Among them, there were 3258 cases with p16(-) and 1907 cases with p16(+). The mean age of patients with p16(+) was significantly older than that of patients with p16(-) . The prevalence of HPV infection was 73.3% (n=2388) in patients with p16(-), whereas it was 84.6% (n=1613) in patients with p16(+) (P<0.001). P16(+) was associated with the infection of high-risk HPV types 16, 33, 52, 56, 58, and low-risk HPV type 81 (P<0.05) Table 1.Each row corresponds to a set of infection genotype(s), and the bar chart on the left demonstrates the size of each set. Each column corresponds to a possible intersection: the filled-in cells show which set is a part of an intersection.3.2Models adjusted for age, gravidity, parity, and cervical histology.3.3Specifically, the risk of p16(+) increased 4.38-fold when infected with HPV33 alone , and 4-fold when infected with multiple high-risk HPV genotypes .3.4In the negative+ group, the risk of cervical lesions above HSIL was 43.06-fold higher than that of the negative group . In the SH+ group, the risk of cervical lesions above HSIL was 93.58-fold higher than that of the SH group . The MH+ group demonstrated the highest risk increase, with p16(+) patients having a 660-fold higher risk of cervical lesions above HSIL compared to the negative group . This group represented the most significant risk for cervical lesions above HSIL. In the other+ group, the risk of cervical lesions above HSIL was 41.54-fold higher than that of the other group . Similarly, in the MO+ group, the risk of lesions above HSIL was 80.91-fold higher than that of the other group .Cervical cancer is unique as it is the only type of cancer with a clear etiology and complete tertiary prevention measures. The two most common ways of screening for cervical cancer are cervical cytology and HPV detection . CytologCountries with established cervical cancer screening programs are increasingly adopting HPV primary screening as the preferred method , 15. EarMultiple infections are common in healthy women (15.8%) but less prevalent in cervical cancer patients (3%-4%), and the relationship between multiple infection and pathogenicity requires further study .In our study, 5165 female patients with definite pathological diagnoses were included, with 1907 exhibiting positive p16 expression and 3258 showing negative p16 expression. P16 expression correlated positively with high-risk HPV types, including HPV-16, HPV-33, HPV-52, and HPV-58, with an increased risk compared to p16(-) cases . Incorporating p16 testing into HPV screening can enhance cervical cancer detection. Further research on multiple HPV infections’ role in cervical lesion development will improve cervical cancer prevention and management.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The paper was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University (2022YJ002). The studies were conducted in accordance with the local legislation and institutional requirements. Informed consent was waived due to the retrospective nature of the study.YZ: Writing – original draft, Writing – review & editing. HBL: Writing – original draft, Writing – review & editing. XL: Data curation, Methodology, Writing – original draft, Writing – review & editing. ZL: Data curation, Writing – original draft, Writing – review & editing. QY: Data curation, Investigation, Writing – original draft. HWL: Data curation, Investigation, Writing – review & editing. ZZ: Data curation, Investigation, Writing – original draft. HY: Writing – review & editing. YS: Writing – review & editing. XZ: Writing – review & editing. YC: Writing – review & editing. JC: Writing – review & editing.


Addiction to online video game streaming has become one of the most appealing ways to occupy leisure time and is one of the most popular activities. The satisfaction it provides and the time invested in it are two of the main reasons why it is preferred. However, despite the clear benefits that this activity offers, in some cases, excessive use can lead to personal and/or family problems or abuse.M = 22.87, SD = 5.02). The Streaming Dependence Scale (SDS) was developed based on a literature review, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted.The objective of the study was to develop and validate a scale to measure potential traits of dependence on online game streaming. The participants were 423 Peruvian adults aged between 18 and 47 years .The scale showed adequate internal consistency . Confirmatory analysis confirmed the one-dimensional structure (χThe brief SDS is a valid and reliable measure that can be used as a useful tool to identify and evaluate streaming dependence. In the age of digital transformation, traditional leisure patterns have undergone a profound metamorphosis. Video games and streaming platforms have become central players in this transformed landscape, altering youth interaction and socialization . This teHowever, video game addiction is an emerging phenomenon that has become increasingly worrisome, given its effects extend to individual aspects disrupting family and social dynamics . Video gVideo game addiction has given rise to an even more worrying phenomenon: the addiction to video game streaming. The popularization of platforms like Twitch, which hosts an average daily audience of 26.5 million viewers, has shown a concerning increase in addiction to these streaming services . In thisVideo game and streaming addiction is not a uniform experience and can vary enormously from one place to another. An example of this is found in Peru, where the use of the internet and video games has risen in recent years, particularly among the youth . DespiteHowever, it is essential to note that although video game and streaming addiction present significant risks, it does not entirely discredit the potential benefits these services can offer. Streaming services can provide significant benefits in terms of learning, skill development, and social support . NeverthTherefore, the aim of this study is to develop and evaluate the psychometric properties of a scale for live-streamed online gaming addiction in adults.M = 22.87, SD = 5.02). The study’s inclusion criteria stipulated that participant had to be over 18 years old, living in Peru, and have regular access to video game streaming platforms. We excluded individuals who did not meet the age and residency criteria, as well as those who did not have regular access to streaming platforms. The majority of participants  was created based on a rigorous literature analysis. This analysis took into account the established diagnostic criteria present in the Diagnostic and Statistical Manual of Mental Disorders, fourth , and fifTo assess anxiety, the Spanish version of the Generalized Anxiety Disorder Scale, GAD-2 , was empThis study faithfully adhered to the principles of integrity, transparency, and respect for human dignity, ensuring the fidelity and accuracy of the findings. The Ethics Committee of a Peruvian university (reference 2181-2022/UPEU-FCS-CF) meticulously examined and approved our research protocol. Each participant was fully and clearly informed about the nature of our study. Informed consent met legal requirements and reflected our conviction in respecting the individual’s autonomy and the right to decide about their participation in the research. Data collection was conducted in person, underscoring to each participant that their involvement in the study was entirely voluntary and anonymous.We began our analysis with a total sample of participants divided into two groups to facilitate robust cross-validation. Sample 1, with 162 participants, served as the basis for developing the model in the exploratory factor analysis (EFA), while Sample 2, made up of 261 participants, was used to validate the model through confirmatory factor analysis (CFA) . A descrTo examine the factorial structure of the SDS, an EFA was performed using unweighted least squares with oblique rotation (promax). Parallel analysis allowed us to determine the optimal number of factors. We verified the suitability of the data with Bartlett’s test of sphericity and the Kaiser-Meyer-Olkin (KMO) coefficient .2), the Confirmatory Fit Index and Tucker-Lewis index (CFI and TLI ≥ 0.95)  , and the ≥ 0.95) . Additio ≥ 0.95) . We evalFinally, we evaluated internal consistency using Cronbach’s alpha coefficient, composite reliability (CR), McDonald’s omega coefficient , and the1All statistical analysis was performed using R software 4.1.1 .M = 1.65), while item 2 had the lowest mean (M = 1.44). In terms of dispersion, it was found that item 6 (SD = 0.65) had a higher dispersion compared to the other items. Skewness (g1) and kurtosis (g2) fluctuated within the acceptable values of ± 1.5 for all items, suggesting a multivariate normal distribution. In addition, it was found that the scale had item-total correlations greater than 0.30, indicating high homogeneity. Finally, an acceptable internal consistency was obtained for each item by calculating the Cronbach’s alpha, with values greater than 0.70 (>0.70).In p < 0.001). Parallel analysis and the scree plot suggested the extraction of a single factor  was carried out on the unidimensional scale to determine the underlying structure of the items. The results indicated an adequate fit of the data through the KMO coefficient (0.83) and the Bartlett’s test of sphericity , SRMR = 0.05] did not reach the standards, indicating that this model might not be the optimal representation of our data structure. In addition, the factor loadings (λ) of items 6 and 8 were below the threshold (>0.50), suggesting that these items might not be strongly associated with the underlying factor. In light of these observations, a second model was developed, taking into account the preliminary evidence provided by the EFA. This analytical step indicated that the goodness-of-fit indices were adequate , thus providing a more robust argument for the validity of our model. Furthermore, factor loadings exhibited satisfactory magnitudes (λ > 0.50), reinforcing our confidence in the role of each item in representing the underlying construct  allowed for the development of the confirmatory factor analysis (CFA) to assess the factor structure . Initialonstruct .In relation to internal consistency  in Model2 = 24.16, df = 13; p = 0.03; CFI = 0.98, TLI = 0.96, RMSEA = 0.06 (90% CI: 0.02–0.09), SRMR = 0.04 (p < 0.001).To evaluate the relationship between the AFC and other constructs, a SEM model was proposed with two latent variables: streaming dependence and anxiety. This model showed a good fit: χR = 0.04 . AdditioThe digital world presents a universe of possibilities and opportunities, but also a vast field of challenges and threats to our physical and mental wellbeing. The use of online games, particularly those streamed live, has witnessed an unprecedented increase, raising concerns related to fatigue, insomnia, anxiety, and depression. The giants of this digital era, such as Twitch and YouTube, have experienced significant growth in their traffic, becoming the primary means of consuming online gaming content. This growing dependence on live-streamed online games on streaming platforms has become an enigma that oscillates between fascination with virtual immersion and fear of digital addiction. However, psychometric evidence supporting the existence of dependence on live-streamed online games, especially in regions like Peru and Latin America, remains scarce and insufficient. In the face of this challenge, the present study aimed to develop and evaluate a new psychometric assessment tool, the Streaming Dependence Scale (SDS).The SDS was designed to capture the nuances of dependence on live-streamed online games in adults. Drawing inspiration from the video game dependence criteria of the The findings of the Exploratory Factor Analysis (EFA) supported a one-dimensional structure, explaining 22.6% of the variance of the construct. However, the low communalities (h2 < 0.30) of items 4, 6, and 8 suggested their removal to improve the model’s robustness .The Confirmatory Factor Analysis (CFA) supported the proposed one-dimensional structure, highlighting the model’s robustness. Although the first model did not show satisfactory fit indices  , the secThe Streaming Dependence Scale (SDS) demonstrated high internal consistency, with McDonald’s Omega (ω) and coefficient H values exceeding 0.70 . This inConvergent validity of the Streaming Dependence Scale (SDS) was also evaluated through the positive correlation between its items and other indicators of the same variable. Average Variance Extracted (AVE) was used as a measure to determine whether the factors explain a significant portion of the indicators’ variance, with an acceptable threshold of AVE greater than 0.5 . In the The findings from our study on the Streaming Dependency Scale (SDS) have implications in several areas. First, from a professional practice perspective, the SDS emerges as an essential tool for mental health professionals. Specifically, when dealing with youth and young adults, the SDS offers an effective means to identify and assess dependency levels, paving the way for timely and effective interventions. Therefore, therapists, psychologists, and other healthcare professionals can use the SDS as a primary assessment tool, enabling them to design appropriate interventions and provide better guidance to their patients. Second, given the rising use of platforms such as Twitch and YouTube, streaming dependency is becoming an emerging public health issue. It is imperative that regulators and lawmakers collaborate with these platforms to formulate preventive policies. These policies can include awareness campaigns, limitations on consecutive streaming hours, and education about the risks associated with excessive use. Third, while theories on digital addiction have previously focused on video games and the Internet, the SDS introduces an additional dimension addressing streaming. This gives us a foundation to theorize about the unique characteristics of streaming, its distinct appeal, and how these factors can contribute to the development of a dependency. Fourth, in the realm of educational practice, the SDS could serve as a valuable resource for educators and school counselors. With the increasing integration of digital resources in the classroom, understanding the potential dependency on streaming can inform instructional design. For instance, educators might be cautious when incorporating streaming platforms as part of their curriculum, being aware of the potential for increased dependency.Moreover, it is crucial to research the applicability of the SDS across different cultural and geographical contexts to ensure its universality. Additional factors, such as real-time social interactions and the relationship between personality, academic performance, social relations, and mental health, should be considered.This study also presents certain limitations that need to be acknowledged. One primary limitation lies in the sample size, especially when advanced analytical techniques are incorporated, which heavily depends on the magnitude of the sample. Various guidelines, such as those proposed by The Streaming Dependence Scale (SDS) offers a valid and reliable tool within the current landscape of digital mental health research. Not only does the SDS allow for a rigorous evaluation of streaming dependence, but it also lays the groundwork for a deeper understanding of how the intrinsic features of live streaming, such as its real-time interactivity and the formation of virtual communities, can influence the onset of addictive behaviors. This understanding, in turn, is crucial for drawing parallels and distinctions between streaming dependence and other recognized forms of digital addiction, like video game addiction or social media addiction. Consequently, it’s imperative to continue research in this direction, not just to assess the prevalence and severity of streaming dependence across various populations and cultural contexts but also to identify associated risk and protective factors. Furthermore, it’s vital to develop, implement, and evaluate evidence-based intervention programs that address both the prevention and treatment of this emerging form of dependence.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study was carried out by the Ethics Committee of the Universidad Peruana Unión (reference 2181-2022/UPEU-FCS-CF). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.LS-S, AC-V, and WM-G participated in the conceptualization of the idea. LS-S and WM-G were in charge of the methodology and software and commissioned the data curation, and resources. All authors contributed the validation, formal analysis, and research, carried out the writing of the first draft, review and editing, visualization, and supervision and have read and approved the final version of the manuscript.


Postmarket surveillance of the incidence of human papillomavirus (HPV)–related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States. Human papillomavirus (HPV) vaccines have been available in the United States since 2006 to prevent HPV-related cancers, which include cancers of the cervix, vagina, vulva, penis, anus, rectum, and oropharynx ,2. The APrevious studies estimated HPV-related cancer incidence from 2012 to 2016 (We used data from the US Cancer Statistics (USCS) 2001-2019 database, which covers almost the entire US population. We included primary cancer cases of HPV-related cancers (variable supplied by SEER*Stat 8.4.0.1), including oropharyngeal squamous cell carcinoma, anal and rectal squamous cell carcinoma, vulvar squamous cell carcinoma, vaginal squamous cell carcinoma, penile squamous cell carcinoma, and cervical carcinoma . The stuThe age-adjusted annual incidence rates for HPV-related cancers from 2001 to 2019 by sex and age group are shown in Using data from the USCS database, we assessed the incidence of HPV-related cancers before and after the introduction of the HPV vaccine. We found that incidence rates for HPV-related cancers were lower in 2015-2019 compared with 2002-2006 among females aged 15-34 years.Reductions in vaccine-type HPV were seen among females aged 14-19 and 20-24 years, 88% and 81% respectively, from 2015 to 2018 compared with prevaccine era rates for those age groups . DecreasA decrease in HPV-related cancers among young males was not observed, likely because of low vaccination rates in this population  and thatA strength of our study is the use of the USCS database, which covers more than 99% of the US population. This study also has limitations. The USCS database does not include information on HPV genotype status in cancer tissue. HPV-related cancers here are based on anatomic sites, and about 80% of them are caused by HPV infections . ImportaIncidence rates for HPV-related cancers decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States. Future studies should continue assessing trends in HPV-related cancers, especially as HPV vaccination coverage has increased across the years, with 75% of adolescents aged 13-17 years having received at least 1 dose in 2020 .pkad016_Supplementary_DataClick here for additional data file.


Age 50 years and over (p < 0.05), having higher education , living in cities with more than 500,000 residents , and no children under 18 in the home  were significantly associated with willingness to vaccinate children against HPV.Since 1 June 2023, a nationwide HPV vaccination program was implemented in Poland. This study aimed to identify factors associated with public awareness of the national HPV vaccination program among adults in Poland and willingness to vaccinate children against HPV. This cross-sectional study was carried out between 14 and 17 July 2023 among 1056 adults in Poland. A self-prepared questionnaire was used. Among the respondents, 51.3% had heard about the free HPV vaccination program. The major source of knowledge on the national HPV vaccination program was TV (62%). Only 31.9% of respondents correctly indicated girls and boys aged 12 and 13 as the HPV-vaccination-eligible population. Willingness to vaccinate children against HPV was declared by 63.3% of respondents. Female gender (OR: 1.42; 95% CI: 1.11–1.81;  Human papillomavirus (HPV) is one of the most common sexually transmitted infections ,2. HPV iThe most effective HPV infection prevention method is vaccination before the initiation of sexual contact ,7. DiffeBetween 2018 and 2019, national recommendations for HPV vaccination existed in 46 of 53 (87%) WHO European Region countries . HoweverIn Poland, HPV voluntary vaccination was recommended for the first time in the vaccination schedule in 2008, with girls aged 11–12 years as an HPV-vaccination-eligible population . As of tSince 1 June 2023, a nationwide HPV vaccination program has been implemented in Poland . The proThere is a lack of scientific data on public awareness of the national HPV vaccination program as well as exposure to health communication campaigns on HPV vaccination and sources of knowledge on HPV vaccination. Most of the previously published data on HPV vaccination in Poland were carried out before the introduction of the universal and free HPV vaccination for children aged 12 and 13 ,23,24,25Therefore, this study aimed to identify factors associated with public awareness of the national HPV vaccination program among adults in Poland and the willingness to vaccinate children against HPV, one month after the introduction of the program.This cross-sectional survey is based on nationwide representative data on public awareness of the national HPV vaccination program in Poland launched on 1 June 2023. Data were collected between 14 and 17 July 2023 among 1056 adults in Poland. A computer-assisted web interviewing (CAWI) technique was used. Data were collected by a public opinion research company  using thThe public opinion research company selected respondents from over 100,000 users of the web-based research platform. The study population was selected based on the non-probability quota sampling methods ,26. The This study was approved by the Ethics Committee at the Centre of Postgraduate Medical Education in Warsaw .The study questionnaire included five questions on public awareness of the national HPV vaccination program, sources of knowledge on the program, willingness to vaccinate children against the HPV, HPV-vaccine-eligible populations as well as the oncogenic potential of HPV.Awareness of the national HPV vaccination program: “Have you ever heard about the free HPV vaccination program implemented as part of the National Cancer Strategy 2020–2030?” (yes/no). Those who said yes were asked to indicate the source of information about the HPV vaccination program (multiple choice question—ten different sources of information). Moreover, all respondents were asked about the HPV-vaccination-eligible population (within the program).Willingness to vaccinate children against HPV: “Would you like to vaccinate your child against human papillomavirus (HPV)?” with a 5-point Likert scale. Respondents who said “definitely yes” or “rather yes” were considered as those who declared willingness to vaccinate children against HPV.The oncogenic potential of HPV: “What do you think are HPV-related diseases? Cervical cancer; vaginal cancer; penile cancer; cancer of the mouth, throat or larynx; laryngeal papillomatosis; anal cancer; genital warts”, each disease with three possible answers: yes/no/I do not know.Sociodemographic variables: Financial status was self-reported (good/moderate/bad), as most of the respondents denied indicating the income per family member. Occupational status was defined based on the question: “What is your current professional status?” . Respondents who indicated bachelor’s degree or completed higher education were defined as those having higher education. The study questionnaire is presented in p < 0.05.SPSS version 28  was used to analyze the data. Frequencies and proportions were used to present the distribution of categorical variables. To compare categorical variables, cross-tabulations, and chi-squared tests were performed. Binary Logistic Regression in SPSS was used to assess the relationships between sociodemographic characteristics (nine different variables) and selected attitudes towards HPV vaccination (separated models: (1) awareness of the national HPV vaccination program; (2) awareness of HPV-vaccination-eligible population; (3) willingness to vaccinate children against HPV; and (4) awareness of the oncogenic potential of HPV). In bivariable analysis, all variables were considered independently. In multivariable regression models, only statistically significant variables in bivariable analysis were included. The odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of the associations. The statistical significance level was based on the criterion Data were received from 1056 respondents aged 18–83 years, 53.2% were females. The characteristics of the study population are presented in Among the respondents, 51.3% had heard about the free HPV vaccination program implemented as part of the National Cancer Strategy 2020–2030. TV (62%) was the major source of knowledge on the national HPV vaccination program. Moreover, more than one-fourth of respondents indicated information on the news portal (23.1%), Internet advertising (20.5%), and radio (20.5%) as the source of knowledge on the national HPV vaccination program . Only 31p < 0.05) declared that they had heard about the national HPV vaccination program. The percentage of respondents who were aware of the HPV vaccination program, eligible population, and declared willingness to vaccinate a child against HPV increased (p < 0.05) with age (p < 0.05) declared that they had heard about the national HPV vaccination program and were aware of the eligible population and declared willingness to vaccinate a child against HPV. Those who were married more often (p < 0.05) declared the correct populations eligible for the HPV vaccination program. Respondents who had children more often (p < 0.05) declared that they had heard about the national HPV vaccination program and were aware of the eligible population and declared willingness to vaccinate a child against HPV. Respondents with passive occupational status (pensioners/students/unemployed) more often (p < 0.05) declared willingness to vaccinate children against HPV. Moreover, respondents with a bad financial status of the family more often (p < 0.05) declared willingness to vaccinate their child against HPV . The percentage of respondents who heard about the national HPV vaccination program was the highest among the youngest respondents (p < 0.05). Respondents with higher education more often indicated radio and news portals as a source of knowledge on the national HPV vaccination program, but less often indicated TV (p < 0.05). Those who did not have children at home more often (p < 0.05) indicated TV and doctors as sources of knowledge about the national HPV vaccination program. Occupationally passive respondents more often (p < 0.05) indicated TV as a source of knowledge about the national HPV vaccination program (The percentage of respondents  who hearcated TV . Those w program .p < 0.01), age 35–64 years (p < 0.05), having higher education , and living in cities above 500,000 residents  were significantly associated with higher odds of hearing about the national HPV vaccination program (p < 0.05) with higher odds of correctly indicating HPV-vaccination-eligible population (girls and boys aged 12 and 13). Age 50 years and over (p < 0.05), having higher education , living in cities with more than 500,000 residents , and no children under 18 in the home  were significantly associated with willingness to vaccinate child against HPV  can benefit from free HPV vaccination. The program was widely promoted in traditional media as well as the Internet . FindingIn Poland, HPV vaccination has been listed in the vaccination schedule by the public health authorities as voluntary vaccination since 2008 . Before The abovementioned studies indicated the low level of public awareness of HPV vaccination and its role in cancer prevention ,23,24. ISmolarczyk et al. , Sypień In Poland, girls and boys aged 12 and 13 are eligible for free HPV vaccination . DespiteThe HPV vaccination coverage rate in Poland is estimated at 7–15% of the eligible population ,21. By 1Practical implications: this is the first analysis of the national HPV vaccination program implemented in Poland since June 2023. Findings from this study revealed that TV is a major source of knowledge on the HPV vaccination program, and more actions are needed to promote this program in social media. Moreover, this study revealed that there were no sociodemographic differences in the exposure to HPV-related social media campaigns, which suggests that personalized communication was not used. Moreover, this study indicated that only one third of adults in Poland are aware of the HPV-vaccination-eligible population, which may lead to misunderstanding and lack of understanding of the patient’s path. This study also showed that most of the adults in Poland were not aware of HPV-related diseases, e.g., penile cancer, anal cancer, and cancer of the mouth, throat, or larynx. Most of the promotional campaigns on the HPV vaccination program in Poland were focused on cervical cancer [l cancer , so moreLimitations: this study was carried out on a nationwide representative sample of adults in Poland, so people without children were also included. Further studies should be carried out among parents of children aged 12 and 13 years (HPV-vaccination-eligible population). The list of sources of knowledge on the HPV vaccination program was limited to the most common ones. Willingness to vaccinate children against HPV was self-declared and medical documentation was not verified (declaration vs. vaccination decision).This study showed that one-third of the adults in Poland have never heard of the national HPV vaccination program. The HPV vaccine is well-accepted by the public, but most of the respondents were not aware of the HPV-vaccination-eligible population despite the implementation of the informative campaign on the HPV vaccination program. The communication strategy for the HPV vaccination program should include personalized communication on social media addressed to parents of children eligible for HPV vaccination. General practitioners should be more involved in promoting HPV vaccination. Education on HPV-related cancers, other than cervical cancer should be included in media campaigns. Lessons learned from the implementation of the national HPV vaccination program in Poland can be used by other countries during the implementation of national HPV vaccination programs.