To investigate the effect of a web-based educational intervention on changing female college students’ willingness and uptake of human papillomavirus (HPV) vaccines, and factors associated with HPV vaccination acceptance in Western and Northern China.chi-square test and Student’s t-test were employed to examine the differences between the intervention and control groups for categorical and continuous data. Logistic regressions were used to analyze factors associated with vaccination intentions.A web-based cluster randomized controlled trial was conducted in Western and Northern China from February to May 2020. A total of 967 female freshmen were recruited from two universities through convenience sampling, stratified sampling , and cluster sampling. Eligible students were randomized into intervention and control group with a 1:1 allocation ratio. The intervention group received seven days of web-based health education regarding HPV and HPV vaccines, whereas the control group received non-HPV-related materials. All students were asked to complete a post-intervention questionnaire to measure their awareness, uptake, and willingness to receive HPV vaccination at 7-day and one-month intervals. The p < 0.001) and knowledge scores  than those in the control group. Similarly, in the intervention groups, willingness to be vaccinated against HPV was significantly higher than in the control groups (p < 0.001). The high cost (57.7%) and concerns about adverse events (56.0%) were the main reasons female college students did not accept HPV vaccines. School location in urban areas, parents’ higher education backgrounds, history of HPV vaccination counseling, history of sexual behavior, and having heard of HPV vaccines were associated with a higher willingness to be vaccinated.Nine hundred forty-six female freshmen aged 18.99 ± 0.63 years were enrolled in the study, with 532 in the intervention group and 414 in the control group. Prior to the intervention, 63.8%, 66.3%, and 60.8% of students had heard of HPV, HPV-related diseases, and HPV vaccines, respectively. Only 2.2% of students reported being vaccinated, but 33.0% were willing to be vaccinated against HPV. After seven days of education, students in the intervention group exhibited higher awareness (Female college students’ HPV vaccination uptake is insufficient, and they have minimal detailed knowledge about HPV and its vaccines. Web-based health education on HPV vaccines is an easy, feasible, and effective way to improve the awareness and acceptance of HPV vaccination among female college students, but it has limited effect on HPV vaccination uptake.The online version contains supplementary material available at 10.1186/s12905-022-01625-0. Cervical cancer is the fourth most frequently diagnosed malignant tumor affecting women's health worldwide, with an estimated 604,000 new cases and 342,000 deaths reported in 2020 . China, Prophylactic human papillomavirus (HPV) vaccination can effectively prevent approximately 70–80% of the corresponding HPV infections and reduce the risk of cervical precancer lesions, cervical cancer, and other HPV-related diseases , 4. SincCollege students are becoming sexually active and are prioritized as HPV vaccination catch-up groups in developed countries such as the United States . PreviouNumerous studies have demonstrated that HPV-related health education can significantly increase awareness of HPV and HPV vaccines, potentially increasing their willingness to receive the HPV vaccine –14. HoweIn the present study, we sought to examine the effect of a web-based educational intervention that affected female college students’ willingness and uptake toward HPV vaccines immediately and one month later, as well as to explore the factors that influence HPV vaccination willingness.This study was a web-based, cluster randomized controlled trial involving a 7-day intervention with a further 1-month follow-up conducted in Western (Sichuan Province) and Northern (Shanxi Province) China between February and May 2020. In each province, one comprehensive university was selected through convenience sampling. After that, six colleges from the university in Sichuan Province and two colleges from the university in Shanxi Province were invited using convenience sampling, stratified sampling , and cluster sampling.Eligible female freshmen were invited to participate in this study. The inclusion criteria were as follows: (1) females aged 18 years or older; (2) first-year undergraduate students; (3) no vaccination contraindications; and (4) having a mobile phone. The exclusion criteria were as follows: (1) males; (2) females under 18; (3) medical students; and (4) previous history of vaccination contraindications.We used the formula Since this study was conducted during the COVID-19 pandemic, all processes were conducted online, including informed consent, baseline survey, intervention, and follow-up survey. Electronic informed consent was obtained from each student before enrollment, followed by an online baseline questionnaire. Furthermore, eligible students were randomly allocated to either the intervention or control group. Random numbers were generated using SAS software version 9.4  to assign each student individually to either the intervention or control group with a 1:1 allocation ratio with majors as a blocking factor.Participants randomly assigned to the intervention group participated in a 7-day intervention and were asked to complete a post-intervention questionnaire to assess their respective knowledge of HPV and HPV vaccines. Students randomly assigned to the control group were provided with educational materials unrelated to HPV prevention during the same period. They were asked to complete the same questionnaire as the intervention group. Additionally, one month after the intervention, students in both the intervention and control groups received a post-intervention questionnaire on the same day. A mobile application collected all data, and the 7-day intervention was administered through intelligent devices, such as a computer or a mobile phone. The study flowchart is presented in Fig. The intervention group received a 10-min daily web-oriented multicomponent education for one week, whereas the control group received some health tips about COVID-19, which was not relevant to HPV vaccination. The intervention covered the accompanying themes: (1) general health education on the prevention of vaccination and sexual health; (2) information on HPV infection and its risk factors, cervix and cervical diseases; (3) presentation of HPV immunization as a preventive measure for cervical cancer; (4) case study showing the prognosis of Chinese women with advanced cervical cancer; (5) storytelling the experience of a female undergrad from being ignorant about HPV to settling on a decision to vaccinate against HPV; (6) information on the best way to improve self-efficacy and self-determination to improve healthy behavior; and (7) social strategies for HPV vaccination, including information on the accessibility and price of HPV vaccine at neighborhood facilities.A self-administered electronic questionnaire in Mandarin was used throughout the study to assess socio-demographic information and knowledge and attitudes toward the HPV vaccine. The research team developed this questionnaire after reviewing relevant literature and conducting several rounds of panel discussions. It has already been used and tested in previous studies employed with different populations. In brief, the questionnaire consisted of four subscales: (1) general information about the study participants, including the participants’ HPV vaccination status, socio-demographic characteristics , and awareness of HPV, HPV-related diseases, and HPV vaccines. (2) perceptions of sexual health education (3 items), including “Have you received sexual health education before the survey?”, “Have you ever had sexual experience?” and “Are you single?” (3) knowledge of HPV and HPV vaccine (7 items) by judging true, false, and don’t know, with a statement including “Persistent HPV infection can lead to cervical cancer.”, “HPV is mainly transmitted through sexual contact.”, “Condoms can reduce HPV infection.”, “HPV infection is almost asymptomatic.”, “HPV infection can cause oral cancer, anal cancer, and genital warts.”, “HPV infection is common.”, “The best time to get vaccinated is before the first debut of sex.” Correct responses for each domain were summed yielding scores of 1 for knowledge of HPV and HPV vaccines. (4) willingness to receive the HPV vaccine (3 items), including “Are you willing to get the HPV vaccine within the next six months?”, “Would you like to encourage your friends to get the HPV vaccine?”, and “What are your main reasons for refusing or discouraging the HPV vaccine?” (Supplementary file 1). In addition, the information in the post-intervention survey was the same as that collected at baseline, except for information on socio-demographic characteristics. The Cronbach’s α value of the questionnaire was 0.816, which achieved good internal reliability.This study was approved by the Clinical Research Ethics Committee of Peking University Cancer Hospital and the Institutional Review Board of the Chinese Center for Disease Control and Preventive and conformed to the Declaration of Helsinki. Prior to implementation, participants were well informed of the purpose, methods, expected risk, and potential benefits of this study. After that, informed consent was obtained from each participant before the baseline survey.chi-squared test for categorical data. Student’s t-test was used for continuous data. Univariate logistic regression was employed to explore the association of potential factors with the willingness to receive the HPV vaccine. Significant parameters found by univariate analysis (p < 0.01) were incorporated and examined using multivariate analysis. Odds ratios (ORs) with corresponding 95% (CIs) were calculated and reported based on Wald chi-square statistics. SPSS statistical software version 20.0  was used to analyze the data in this study. Statistical significance was assessed by two-tailed tests with an α level of 0.05.Categorical data were assessed using case counts and percentages; continuous data, including age and knowledge of HPV vaccine scores, were presented as the mean and standard deviation (SD). Differences between the intervention and control groups and awareness of the HPV vaccine at baseline and post-intervention were analyzed using the Nine hundred sixty-seven female college students from two schools were surveyed between February and July 2020. Of these participants, 21 were excluded due to they had received HPV vaccination before the survey. 946 eligible students were enrolled and randomly divided into the control and intervention groups. More than half  of the enrolled students were in the intervention group and received online health education about HPV and HPV vaccines for seven days. Immediately after the intervention and one month after the intervention, a total of 810 and 820 students completed the post-intervention questionnaire, respectively   majored in science. The majority of the participants were ethnic Han Chinese (93.0%). A total of 75.5% had lived in urban areas for more than 1 year, and 69.7% of them had monthly living expenses between 1,000 and 2,000 Chinese Yuan (CNY). A total of 35.7% of the students had parents with junior high school or below, 29.5% with senior high school, and 34.9% with a bachelor's degree or above. Furthermore, 79.0% of students had ever received sexual education or knowledge, and 35.1% reported having searched or consulted for HPV vaccines. The vast majority (98.2%) of the students had not had sex, and 84.8% were single. There was no statistically significant difference in general demographic characteristics between the intervention and control groups, except for receiving sexual education or knowledge before the survey .Table p < 0.001). In addition, the knowledge score regarding HPV and HPV vaccines was considerably higher in the intervention group than that in the control groups . However, the correct rates of "HPV infection is almost asymptomatic" (21.2%) remained low.After the intervention, awareness of HPV, HPV-related diseases, and HPV vaccines in the intervention arm were significantly higher than control arm  of students had received HPV vaccines, and 33.0% (312/946) and 68.8% (651/946) were willing to be vaccinated or willing to encourage their friends to get vaccinated. After the intervention, willingness to be vaccinated and desire to encourage others to take HPV vaccines increased from 36.3% to 45.6% and 71.2% to 84.4%, respectively, in the intervention group. However, the number of vaccinated students remained low, with only 1.6% and 1.8% in the control and intervention groups, respectively  and the safety and efficacy of the vaccine  than the control group, but the high price remained the main factor for students to refuse HPV vaccination (Table The high cost of vaccination (57.7%) and concerns about adverse events (56.0%) were the main reasons for reluctance to be vaccinated at baseline. After the intervention, students in the intervention group had significantly fewer concerns about adverse events  and students with highly educated parents  were more likely to be vaccinated against HPV. In addition, students who had consulted regarding HPV vaccines  had previous sexual experience  and had heard of HPV vaccines  were more likely to receive the HPV vaccination. Six factors, including residence place, living expenses, sexual education history, current relationship, heard of HPV, and HPV-related disease, were excluded from the multivariable logistic regression model  , Hong KoHPV vaccination is relatively expensive for most college students in the presented study, which leads to various affordability issues with the increasing demand for HPV vaccination. Currently, the available imported bivalent, quadrivalent, and 9-valent HPV vaccines in the Chinese mainland cost about 600 CNY, 800 CNY, and 1,300 CNY each dose, respectively, and are too expensive to afford for most college students . Besidesp = 0.010) before health education, which may underestimate the effect of the intervention. Last, the study was conducted during the COVID-19 outbreak, and there were barriers to HPV vaccination, resulting in no significant behavioral changes observed in this study.Nevertheless, the study has several limitations. First, this study enrolled only two universities from two cities, which cannot accommodate representative female college students in Western and Central China. Future studies with broader coverage and larger sample sizes are needed to provide evidence for HPV vaccination promotion. Second, since all questionnaires were self-reported, some results should be interpreted with caution, especially questions about sexual activities. Third, all students in the intervention group were included in the post-intervention analysis but did not assess the completion and quality of student learning, thus potentially underestimating the effect of the intervention. Fourth, a significantly higher proportion of students in the intervention group had received sexual health education than in the control group (81.8% vs. 74.9%, In summary, female college students’ HPV vaccination uptake is deficient, and they have minimal detailed knowledge about HPV and its vaccines. Web-based health education on HPV vaccines is an easy, feasible, and effective way to improve the awareness and acceptance of HPV vaccination among female college students but does not change vaccination behavior. Further studies are needed to explore suitable HPV vaccine intervention strategies for female college students and improve HPV vaccination rates in the Chinese mainland.Additional file 1. The questionnaire used in this study.


Cervical cancer can effectively be prevented by human papillomavirus (HPV) vaccination and early detection and treatment of precancerous lesions (screening). Nevertheless, cervical cancer remains a global public health problem and an important threat to women’s health worldwide. It is the fourth most common cancer in women with more than 600,000 cases and 342,000 deaths in 2020 . ApproxiCervical cancer screening has traditionally been based on detection of cytological abnormalities in cervical cell samples, so-called cytology-based screening. This method has effectively reduced cervical cancer incidence in high-income countries when implemented in organized programs , 4. HoweDuring the past two decades, HPV testing has emerged as a new and highly effective screening method against cervical cancer. Randomized trials in high-income  and middUntil now, there has been limited evidence on the real-world performance of HPV testing for cervical cancer screening in middle-income countries . In thisTo our knowledge, the study by Zhao et al. is the largest to date on the performance of HPV testing versus cytology for cervical cancer screening in a middle-income country. In line with findings from high-income settings , 7, 8, tInterestingly, Zhao et al.  also perThe findings of Zhao et al. provide strong support for implementing HPV-based screening in China and other middle-income countries. In addition to its excellent sensitivity, an advantage of HPV testing is the high and long-lasting negative predictive value, permitting an extension of screening intervals to 5 years or more , 4. FurtAlthough the advantages of HPV testing are well-documented, practical implementation of an HPV-based screening program can pose substantial challenges. Policy-makers planning to implement HPV-based screening face multiple choices regarding program design, including choice of HPV test, triage method, follow-up and referral recommendation, target age range, screening interval, communication strategy, and training strategy for health care providers . The optThe study by Zhao et al. provides further evidence for the benefits of HPV-based cervical cancer screening in middle-income settings. Introducing HPV-based screening in countries around the world is a crucial step to achieve the global goal of cervical cancer elimination, potentially saving the lives of thousands of women worldwide.


The 5-year relative survival for patients with head and neck cancer, the seventh most common form of cancer worldwide, was reported as 67% in developed countries in the second decade of the new millennium. Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Recently, liquid biopsy monitoring of the molecular fingerprint of head and neck squamous cell carcinoma has been proposed and investigated as a strategy for longitudinal patient care. These innovative methods offer rapid, safe, and highly informative genetic analysis that can identify small tumors not yet visible by advanced imaging techniques, thus potentially shortening the time to treatment and improving survival outcomes. In this review, we provide insights into the available evidence that the molecular tumor fingerprint can be used in the surveillance of head and neck squamous cell carcinoma. Challenges to overcome, prior to clinical implementation, are also discussed. Head and neck malignancies encompass a diverse group of aggressive tumors arising at the epithelium of the upper aerodigestive tract mucosal linings, squamous cell carcinoma being the most frequent histopathological type (90%). Head and neck squamous cell carcinoma (HNSCC) has been associated with external risk factors such as smoking habits, alcohol consumption, and infection with herpes papillomavirus (HPV) or Epstein-Barr virus (EBV), all of which are reflected in the genomic and transcriptomic profiles of their respective factor-based subtypes ,2,3,4,5.The 5-year relative survival rate for head and neck tumors improved from 53% in the 1970s to 67% in the 2010s in the USA . DespiteMonitoring minimal residual disease and disease dynamics is of paramount importance to the timely detection of recurrence, as awareness when the tumor burden is minimal can maximize the efficacy of salvage treatment and improve survival ,11. CurrRecent studies have demonstrated that body fluid-based diagnostic methods offer real-time monitoring during follow-up , aiding ctDNA consists of DNA fragments that are released from tumor cells into biological fluids including blood, saliva, cerebrospinal fluid, and urine . While cDetermining HPV status is of critical importance in the diagnosis and management of HNSCC, as HPV-positive tumors have unique pathological and clinical characteristics with implications for prognosis and treatment decisions. Generally, HPV-positive tumors are susceptible to radiation and anticancer drugs, and thus have a better prognosis  as compared to HPV-negative tumors . This im® DNA blood test currently available in the United States . The company is currently working on a saliva-based version of the test, for which results matching those of the blood-based assay were presented at the American Society of Clinical Oncology 2021 annual meeting [Recently, Chera and colleagues performed a prospective biomarker trial of patients with non-metastatic HPV-associated (p16-positive) OPSCC . Partici meeting .Several studies have detected the presence of EBV in HNSCC in specific regions of the world (Southern China and Southeast Asia), implying its possible role in the development of malignancies throughout the upper aerodigestive tract, with most cases presenting at the nasopharynx ,36. The Similar to HPV, EBV ctDNA has also been recognized as a promising biomarker with the potential for accurate early detection of nasopharyngeal carcinoma (NPC) recurrence ,43,44,45In line with these reports and given that up to 66% of recurrences are being missed when following the previous National Comprehensive Cancer Network and European Society for Medical Oncology (ESMO) guidelines, the most current ESMO guidelines published in 2020 recommend evaluating EBV ctDNA at least every year ,47.Gene- and pathway-focused sequencing initiatives have shed light on our understanding of the molecular pathogenesis of non-viral-driven HNSCC. These studies have shown that non-viral HNSCC is broadly driven by non-mutually exclusive mutations in genes involved in four pathways: cell survival and proliferation , cell-cycle control (CDKN2A and CCND1), cellular differentiation (NOTCH1), and cellular adhesion and invasion signaling (FAT1) ,48,49. MThe groundwork for surveillance clinical tests for the early detection of HNSCC recurrence based on tumor-shed DNA mutations was laid by Wang and colleagues . These rAs whole-genome sequencing becomes more accessible, large sequencing efforts such as The Cancer Genome Atlas initiative have been key for detecting additional alterations specific to the pathogenesis of HNSCC tumors. Some genes that have been identified this way include members of the TRK family , MAPK pathway (MAPK1 and NF1); genes implicated in chromatin regulation ; genes of the NOTCH, Hedgehog, and Wnt pathways; apoptosis genes (CASP8); and genes involved in DNA repair  ,54. The Recently, Cui and colleagues  improvedIn an effort to encompass as many tumor-related alterations as possible, Mes and colleagues  analyzedAs compared to the detection of HPV or EBV ctDNA sequences after cancer treatment, specific genetic lesions are not as specific for predicting tumor recurrence. For example, pathogenic mutations for TP53 have been reported in oral rinses from both cancer patients and non-cancer controls , therebyIn addition to mutations and CNAs, methylation of circulating DNA has also been employed as a liquid biomarker. DNA methylation is an epigenetic mechanism of gene expression control, and its dysregulation has been reported in various cancers, including HNSCC. Methylation signatures of circulating DNA have proven useful in the detection and classification of different cancer types at diagnosis ,62, and Aberrantly methylated copies of the SHOX2 and SEPT9 genes are among the liquid biopsy methylation biomarkers with the highest level of validation regarding their clinical performance . After eMultiple studies have explored the coding and non-coding transcriptome of HNSCC cancers in a systematic manner ,71,72. TTumor-derived RNA has been identified in different body fluids , and could serve as a biomarker for disease diagnosis and stratification, detection of minimal residual disease, and determination of prognosis. The past decade has produced myriad reports describing blood- and saliva-based RNA expression in HNSCC. For HPV-positive tumors, HPV16 E6/E7 ctRNA expression in circulating tumor cells has proven useful as a biomarker for clinically relevant HPV infection in HPV-positive OPSCC . In addiAlthough RNA-based liquid biomarkers have received attention for recurrence/therapy response monitoring in several cancer types ,84,85, tWith high rates of recurrent disease, the five-year relative survival of HNSCC has reached 67% . TreatmeSince the most predominant oncogenic virus in head and neck cancer is HPV, several proofs-of-concept have been published on longitudinal measurements of HPV ctDNA in the saliva and/or plasma of HNSCC patients, demonstrating success in identifying tumor recurrence months earlier than other surveillance techniques ,43,44,46Recurrence detection by means of liquid biopsy definitely has several advantages, including the possibility of rapid initiation of second-line treatments, which is potentially associated with improved outcomes and increased survival chances. In addition, rapid recurrence detection may further aid in the usage of personalized medicine approaches, which are quickly gaining interest in the clinics . Neverthhttps://naveris.com/what-is-navdx/ accessed on 23 December 2021). Furthermore, the few treatment options available for when the tumor is not yet detectable by imaging techniques also limit the clinical implementation of these biomarkers. An integrated approach, using a panel of markers in both blood and saliva, might be the optimal way to predict recurrence with the highest sensitivity and specificity. Finally, very few authors have reported on the cost-effectiveness of liquid biopsies in clinical practice [Despite these developments in liquid biopsy analysis, there is still a lack of implementation in clinical practice. This is in part due to the wide variability in methods used and often-small sample sizes, or a focus on a very specific subset of patients. Although there is a validated HPV ctDNA blood test available for the detection of HPV-driven cancer, it is currently available only in the United States (practice . All of In conclusion, the studies highlighted here clearly indicate that liquid biopsy-based, non-invasive biomarkers can play an essential role in the detection and management of early recurrence of HNSCC. Further standardization and exploration of novel treatment options will be essential to unlocking the full potential of these fluid-based biomarkers.


Candida vaginitis on this infection. From 11 August 2017 to 11 September 2018, 12,628 outpatient participants ranged from 19 to 84 years old were enrolled and analyzed. HPV DNA was amplified and tested by HPV GenoArray Test Kit. The vaginal ecology was detected by microscopic and biochemistry examinations. The diagnosis of Candida vaginitis was based on microscopic examination  and biochemical testing  for vaginal discharge by experts. Statistical analyses were performed using SAS 9.4. Continuous and categorical variables were analyzed by t-tests and by Chi-square tests, respectively. HPV infection risk factors were analyzed using multivariate logistic regression. Of the total number of participants, 1753 were infected with HPV (13.88%). Females aged ≥ 40 to < 50 years constituted the largest population of HPV-infected females (31.26%). The top 5 HPV subtypes affecting this population of 1753 infected females were the following: HPV-52 (28.01%), HPV-58 (14.83%), CP8304 (11.47%), HPV-53 (10.84%), and HPV-39 (9.64%). Age  and alcohol consumption  were found to be risk factors for HPV infection. However, the presence of Candida in the vaginal flora was found to be a protective factor against HPV infection . Comparing with our previous study of 2016, we conclude that the subtype distribution of HPV infection is relatively constant in Changsha. Our data suggest a negative correlation between vaginal Candida and HPV, however, more radical HPV management is required in this area for perimenopausal women and those who regularly consume alcohol.This cross-sectional study investigated the characteristics of cervical HPV infection in Changsha area and explored the influence of  Nearly 989,000 new cases of CC are diagnosed in China every year, and the overall hrHPV infection rate in mainland Chinese women is 19.0% 2. The top 5 hrHPV subtypes with the highest infection rates in China include HPV-16, HPV-52, HPV-58, HPV-53, and HPV-183. HPV infection is most prevalent among childbearing-age and menopausal women; the prevalence among menopausal women is known as the “second-peak”4. Some of the factors reported as closely correlated with HPV infection include alcohol consumption, smoking, age at first marriage, marital status, vulvovaginal ulcers, and vulvovaginal inflammation6. The biological mechanisms of risk factors on HPV infection are less well understood over the decades. However, these investigations have yielded few results when it comes to the pathogenesis of this infection.Human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection in women. Persistent infection with high-risk HPV (hrHPV) subtypes, but not all HPV infections, can lead to the development of cervical cancer (CC), a disease that adversely affects the health of women worldwide7. Lactobacillus maintains a low vaginal pH value through producing lactic acid to perform HPV protection8, and Candida stimulates T cell proliferation to against HPV infection9. However, Gardnerella, Fusobacteria, Mycobiota, and Chlamydial trachomatis (CT) were associated with HPV infection11, for example, CT plays as the entryway of the cervical epithelium and facilitate HPV infection11.In recent years, scientists have become interested in and made promising progress investigating the mechanisms of vaginal flora. Some studies have reported that vaginal microorganisms might promote or impede HPV infection by infecting a host’s cervical micro-ecological environment, and may further play essential roles in the pathogenicity of HPV and cervical lesions12. However, more evidence and investigation need to be updated to analyze the longitude development of cervical cancer prevention and treatment in Changsha. Many risk factors of cervical cancer include lifestyle such as smoking, HPV type and distribution, and the influence of vaginal flora on HPV need to be updated. We examined patients that attended the Physical Examination Outpatients Center at our hospital and hypothesized that the distribution of HPV might have changed in the few years since this previous study. We also hypothesized that vaginal flora or Candida might play a vital role in influencing this infection.In 2016, Xiao et al. reported on the characteristics of HPV infection in Changsha based on information obtained from the Gynecological Outpatient Center of our hospital Candida infection (P < 0.001), age at first marriage (P < 0.001), age at first childbirth (P < 0.001), and alcohol consumption (P = 0.003). Additionally, there were no significant differences between the two groups in BMI (P = 0.855), white blood cell (WBC) count (P = 0.873), neutrophil percentage (P = 0.298), lymphocyte percentage (P = 0.199), fasting blood glucose (P = 0.199), vaginal H2O2 (P = 0.199), vaginal grades (P = 0.227), vaginal trichomonas (P = 0.482), age of menstruation onset (P = 0.874), whether they had given birth (P = 0.106), diet [including spicy diet (P = 0.224) and sweet diet (P = 0.716)], smoking (P = 0.299), daily sitting time (P = 0.748), and waistline measurements (P = 0.704) . There were significant differences between the HPV-negative and -positive participants in mean age , vaginal pH , vaginal samples positive for galactosidase (P < 0.001), sialidase, leukocyte esterase (P = 0.001), and We analyzed the age distribution of the study participants. The highest positive infection rate of HPV was 31.26% in 40–49.9 years old group , followed by 27.44% in 30–39.9 years old group (n = 481), and 24.59% in 50–59.9 years old group (n = 431). This data showed the HPV distribution of different age groups , HPV-58 , CP8304 , HPV-53 , and HPV-39 , respectively. These results are strongly consistent with previous research performed at our hospital; 28.01%,u) and the adjusted OR (ORa) were found to be consistent. The risk factors of HPV infection were age  and alcohol consumption . However, vaginal Candida infections , age at first marriage , and age at first childbirth  were protective factors against HPV infection in the study. Additionally, the age at first childbirth ≥ 20 to < 30 years  was also found to be protective against HPV infection, but the difference was not significant (P = 0.38) . The AUC values for all these variables were found to be approximately 0.8. Additionally, the ANOVA test and the initial models that included all variables produced results that were not significant, which indicates that the statistics using AUC were reliable. As an example, the largest AUC as a predictive factor for HPV infection was that of vaginal Candida infection. This AUC value was 0.881, the optimal cut off value was 0.164, the sensitivity was 1.000, and the specificity was 0.827  were significant at vaginal 3. In our study, the top five HPV subtypes were the following: HPV-52, HPV-58, HPV-CP8304, HPV-53, and HPV-39. However, the top 5 subtypes found in the study of Xiao et al., performed at the same hospital as our study, were HPV-52, HPV-16, HPV-58, HPV-CP8304, and HPV-5312, and the top 5 HPV subtypes found in China overall were HPV-16, HPV-52, HPV-58, HPV-53, and HPV-183. The detection results of our hospital in recent five years showed that the positive rates of hrHPV and HPV16 were lower than the past and the national average level, indicating that Changsha city has achieved good results in reducing the high risk of HPV16 and related cervical precancerous lesions. The HPV-CP8304 is a popular subtype in our region with high prevalence but low risk. Our data were predominately consistent with the previous investigation12 and mostly in line with the analysis of national data3. These differences may be a result of variable geography, ethnicity, education, and horizontal health care. However, when considering vertical health care, this decrease in HPV infection evident in our study may be explained by improvements in women's health care and the improvements in awareness of women's health in recent years14.The overall HPV-positive rate of this study was lower (13.88%) than that of the overall in mainland Chinese women (19.0%)16. In 2015, Wang et al., confirmed that the hrHPV rate was 91.8% patients with invasive cervical cancer (ICC) in Hunan province17. Also, HPV-16 and HPV-18 are considered the top hrHPV subtypes worldwide20, However, neither HPV-16 (6th) nor HPV-18 was identified as a prevalent subtype in our study. Several factors may account for this, such as regional differences, improvements in women's health care, and the awareness of women's health. Another reason is the participants involvement differences between studies. We investigated women from the Physical Examination Outpatient Center from our study while others from the Gynecological Outpatient Center. Symptomatic or sick patients would generally choose the Gynecological Outpatient Center for CC screening, while the Physical Examination Outpatient Center encounters more asymptomatic or healthy cases. Taking this into account, although our data is reasonably consistent with previous studies, the differences were unavoidable. These screening sample differences also suggest that the CC screening at physical examination outpatient centers, rather than the gynecological outpatient centers, might receive a closer result compared to the rate of HPV infection across the whole country.Persistent hrHPV infection was believed as the causative agent in over 90% CC in early in 2000 by Bosch et al.21. Several factors might contribute to this pattern, including that immunity decreases with age, meaning that older women are at an increased the risk of developing HPV infections22. Besides, the postmenopausal population have elevated pH values due to the decreased estrogen levels that is correlated to the low glycogen levels and Lactobacillus abundance, making them sensitive to HPV infection24. Additionally, older women tend to seek out for routine gynecological care and cancer screenings25, which potentially elevates the HPV-positive rate for this age group. This explains our finding that increased age may be a risk factor for HPV infection  . This might be explained that the sialidase, one of the virulent biomarkers of Gardneralla vaginalis, that through hindering the epithelial biofilm formation, facilitates the infection/co-infection of HPV and other microorganisms , herpes simplex virus (HSV), human cytomegalovirus (HCMV)35. In line with the study of Lili et al., that the leukocyte esterase positive rate is higher in the HPV-positive group when compared with that of the HPV-negative 36. We then figured out that alcohol consumption was correlated with HPV infection. An underlying reason for this could be that alcohol may increase sexual disinhibition, which results in increased unsafe sexual behaviors38. Smoking is another potential risk factor. Multiple studies have posited that both passive and active smoking of cigarettes increase the risk of developing HPV infection, as smoking suppresses innate immunity and can cause structural and functional changes within the respiratory system41. However, our data found no significant correlation between smoking and HPV infection. This is possibly due to limited case numbers of HPV-infected participants and the relatively restricted region within which participants lived.We also investigated potential risk factors of HPV infection. Our data showed that the vaginal pH of the HPV-positive group was significantly elevated than that of the HPV-negative group , this might due to the vaginal dysbiosis, and particularly with the displacement of 6. This phenomenon might be explained by the notion that older women are more likely to engage in safe sexual behaviors6. Additionally, older women are believed to have greater awareness of genital hygiene and healthcare, which reduces the rate of HPV infection42. The vaginal Candida infection was significantly negatively correlated with HPV infection . This might be due to the presenting symptoms of Candida vaginitis, such as leukorrhea, vulvar pruritus, dyspareunia, and dysuria43, encouraging patients to seek timely gynecological screening. Additionally, Candida parapsilosis can serve as a biofilm on the surface of the genital tract, which may act as a shield against invasion by other microorganisms44. Liang et al. also supports this result; they reported similar findings of Candida albicans being protective factor against HPV infection 45. Engberts et al. also reported that infection by Candida does not increase the risk of developing CC46. Additionally, Gonia et al. found that Candida parapsilosis protects premature intestinal epithelial cells from invasion and damage by other microorganisms47. Wang et al. also reported that Candida albicans can enhance T cell proliferation, which might play a vital role in regulating the local vaginal and cervical microenvironments, and further inhibit the pathogenicity of HPV infection and cervical lesions9. However, the mechanisms that mediate the relationship between Candida infections and HPV infection remain controversial. Studies of larger sample sizes and further investigations are required to explore these mechanisms.Meanwhile, the probable protective factors were summarized. Our study found that a marriage age of 20 years or older (OR 0.79) and an age at first childbirth of 30 years or older (OR 0.67) were protective against HPV infection (P < 0.05). Consistent with these findings, Niyazi et al. reported that early marriage might be a risk factor for hrHPV infectionGonorrhea, Syphilis and HIV that might infect the vaginal-cervical microbiota49. There are further constraints in our study that might limit its wider applicability. We neither investigate details of alcohol consumption, nor follow up on infection persistence, progression, or the outcomes of participants. Besides, our documented vaginal microecology narrowly focused on Candida of different fugal types, more preliminary clinical findings need to be further studied, with the rest of vaginal cofounders, such as Gardnerella, Fusobacterium, bacterial vaginosis and aerobic vaginitis50. Furthermore, we excluded the previous positive HPV patients with or without local drug administration which might bias its distribution. Additionally, we did not further investigate the participants infected by multiple subtypes of HPV.Some deficiencies cannot be ignored for this study. Besides the limited number of HPV cases and lack of information regarding participants’ marital status, number of sexual partners, use of oral contraceptives, and the history of sexual transmitted infections (STIs) such as Candida with HPV infection in Changsha, Hunan. Our findings potentially provide valuable information to assist in the improvement of clinical HPV screening and CC prevention in local regions. To improve future research, larger sample sizes, optimization of the participant questionnaire, improved follow-up of participants, and in vitro experimentation might be considered.Despite these limitations, our study is in strong agreement with previous research. Additionally, this study is the first to explore the potential relationship between vaginal Candida infection is a protective factor against HPV infection and that more radical HPV management is required in the local Changsha area for perimenopausal women and who regularly consume alcohol.In conclusion, we found that the prevalence of HPV infection and the distribution of its subtypes is relatively constant in Changsha, Hunan. Our data suggest that vaginal Every female patient that attended the Physical Examination Outpatients Center at the Third Xiangya Hospital of Central South University between 11 August 2017 and 11 September 2018 was asked to complete a questionnaire and voluntarily sign written informed consent. This study was approved by the ethics committee of the Third Xiangya Hospital of Central South University (IRB No. 20017). All methods were carried out in accordance with relevant guidelines and regulations.To be included in this study, participants had to satisfy all of the following inclusion criteria: (1) age ≥ 18 years old and no previous positive HPV results; (2) no sexual intercourse, vaginal douching, or administration of vaginal medications in the 3 days before vaginal samples taken; (3) mentally competent so as to understand the consent form and communicate with study staff. The exclusion criteria: (1) history of no sexual activity; (2) HPV positive results in one year or a history of CC; (3) received a hysterectomy; (4) received treatment for vaginitis in the past 3 months; (5) had sexual intercourse, vaginal douching, or taken vaginal medication in the 3 days before vaginal samples taken; (6) unable understand the consent form and communicate with study staff; (7) the pregnant; (8) withdraw from the study.2O2-negative/positive; Candida-negative/positive; Trichomonas-negative/positive; grades-I/II/III/IV  and low amounts of Lactobacillus species, mainly L. iners. Finally, Grade IV is characterized by the presence of a variety of Streptococcus spp.)52 were carefully recorded and double-checked by two research assistants.Patient data extracted from medical records, including general information  and test results  and vaginal microecology test results which were diagnoses by experienced cytologist  and biochemical testing  for vaginal discharge by experts. In our study, the criteria of bacterial infection diagnosis by Amsel method are as follows: (1) uniform vaginal secretion; (2) pH > 4.5; (3) amine smell in secretion with 10% potassium hydroxide; (4) positive laboratory test results (Gram staining for bacteria in secretion or wet film for clue cells). If any three of the above criteria are met (but the last one is necessary), the diagnosis can be made.The vaginal and cervical samples were collected by gynecologist, while the blood was drawn by nurse. All vaginal samples were collected for the test of vaginal microecology, the cervical samples were collected for HPV screening, and the blood samples were collected for lab testing. The Pentaplex Vaginitis Detection kit  was used for vaginal ecology testing, including galactosidase, sialidase, leukocyte esterase, HA total of 12,628 participants with complete medical records were enrolled in this study and retrospectively analyzed; 10,875 were non-HPV infected females and 1753 were HPV-infected females .53.HPV DNA was amplified by polymerase chain reaction (PCR). Then, HPV genotyping by HybriMax was performed using an HPV GenoArray Test Kit . This assay can determine 21 HPV types, including 14 high-risk HPV types , five low-risk HPV types , and two unknown-risk types (53 and CP8304), by the flow-through hybridization technique using HPV DNA amplified by PCRStatistical analyses were performed using Statistical Analysis System 9.4 . Continuous variables were analyzed by t-tests, and the categorical variables were analyzed by Chi-square tests. The age distribution and subtypes distribution were summarized based on HPV positive cases.The multivariate logistic regression risk model was used for investigating the risk and protective factors of HPV infection. The risk factor was defined as odds ratio (OR) > 1 and the protective factor was OR < 1. The multivariable regression model was established in three steps. Firstly, univariate analyses were performed to demonstrate which patient variables correlated with the presence of HPV infection with a significance of P < 0.05, and the analysis of variance (ANOVA) test and all variables were significantly different in the model (P < 0.05). Next, non-significant variables (P > 0.05) were removed, and stepwise regression was performed using the forward and backward method. Finally, the variables demonstrated as significant (P < 0.05), including age, a vaginal microecology test sample positive for fungal infection, age at first sexual intercourse, age at first childbirth, and alcohol consumption were included in the model. Analyses were performed using tenfold cross-validation, that the data set is divided into 10 parts, including 9 parts as training data and 1 part as test data. The final data is generated area under the curve (AUC) values of the receiver operating characteristic (ROC) curves. This was then used to determine the model's classification ability, and AUCs were compared to assess prediction accuracy. A P value of < 0.05 was considered statistically significant.The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.Supplementary Information.


The objective of this study, the first of its kind in Kosovo, is to determine the level of Kosovo women’s knowledge and awareness of HPV infection, HPV vaccination, and its relation to cervical cancer.This cross-sectional study was conducted from July to October 2018 at the Clinic of Obstetrics and Gynecology at the Hospital and University Clinical Service of Kosovo.Out of 800 questionnaires distributed, 645 were completed and returned (80.6%). Only 0.5% of women were vaccinated against HPV. The majority of respondents (66.4%) had no previous knowledge of HPV (human papillomavirus). Only 27.6% of respondents were aware that HPV is responsible for cervical cancer. About two-thirds (70.1%) of respondents had never heard of the HPV vaccine, and only 24% knew that the HPV vaccine can prevent cervical cancer.The level of vaccination against HPV and the level of knowledge and awareness of HPV infection is extremely low. Higher education, younger age, and living in an urban area were favorable factors and correlated with awareness of HPV infection, vaccination against it, and its relation to cervical cancer. Based on this study, there is an immediate need for developing an educational program on HPV infection and the importance of HPV vaccination as a preventative measure against developing cervical cancer.The online version contains supplementary material available at 10.1186/s12905-021-01496-x. Genital human papillomavirus (HPV) is one of the most frequent sexually transmitted infections. Although more than 200 genotypes of HPV have been identified, a group of 15 high-risk types are known as an essential factor for development of cervical cancer, 4.The worldwide prevalence of HPV infection varies from 2 to 44% . SeveralIn order to prevent HPV infection and thus reduce the risk of precancerous lesions and HPV-related malignancies, three types of vaccines are in use worldwide. The bivalent vaccine (Cervarix) targets HPV 16 and HPV 18. Quadrivalent Gerdasil covers HPV 16, HPV 18, HPV 6, and HPV 11, and the last vaccine to be licensed in US and Europe, mainly in high-income countries, is nonavalent Gerdasil 9, which offers protection against HPV 16, 18, 31, 33, 45, 52, 58, 6, and 11.By 2017, 71 countries (37%) had introduced the HPV vaccine into their national immunization program for girls, and 11 countries (6%) had also done so for boys . The WHOA study by Klug et al. showed that awareness of HPV across all populations is poor . Many heAs a small low-income country, Kosovo has not yet established any organized screening program for cervical cancer or vaccination against HPV. The prevalence of HPV among Kosovo women is approximately at the same level as in other countries in the region, and so the risk for acquiring HPV-related malignancies is very high. Therefore it is necessary to introduce application of the HPV vaccine as well as the development of related health-promotion programs.This cross-sectional study was conducted from July to October 2018 at the Clinic of Obstetrics and Gynecology at the Hospital and University Clinical Service of Kosovo. The methodology was based on questionnaires containing relevant indicators for each attribute. On average, the clinic serves about 200 hospitalized patients and provides outpatient treatment or advice to approximately 50 patients on a daily basis. This is the only tertiary clinic in Kosovo, and it provides medical services to women from across the country.During the study, 800 structured questionnaires were distributed to women that were hospitalized or had consultations at the outpatient unit between July and October 2018. The pretested questionnaire had three parts. The first part elicited socio-epidemiological data including the age, place of living  level of education as well as sexual activity of the women. The second part tested women’s knowledge of HPV infection, the HPV vaccine, and its relation to cervical cancer. The third part of the questionnaire gathered information regarding women’s knowledge and the rate of cervical cancer screening (the Pap test), also in the end specifying the source of information regarding all the issues of interest in our study.The questions were simple to answer, with only one correct response. The questionnaires were completed by respondents and then gathered at the collection point in nurses’ offices in the departments at the clinic. Out of 800 questionnaires, 645 were completed properly and returned. The remainder were not filled out correctly or were not returned for final analysis. The overall response rate was 80.6%.For more details regarding the questions find the questionnaire attached to the manuscript.P values < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS, v. 26.Categorical variables were described by frequencies and percentages, and continuous variables by means and standard deviations. Multivariable logistic regression was used to study the association between demographic, social, and informative factors and awareness about the cause and prevention of cervical cancer, as well as the association between demographic, social, and informative factors and understanding the cause and prevention of cervical cancer. Out of 800 questionnaires distributed, 645 were completed correctly (80.6%). Out of this number, 295 respondents (45.7%) belong to the age group 18–25, followed by 187 (29%) in the age group 26–33. Only four (0.6%) respondents were older than 58. Regarding their place of residence, 345 (53.5%) of women lived in urban areas, and 300 (46.5%) lived in rural areas. According to level of education, the respondents were divided into four different groups: 268 (41.6%) had completed secondary school, 212 (32.9%) had a bachelor’s degree, 126 (19.5%) had finished elementary school (or less), and only 39 (6.0%) had a master’s degree or higher level of education  stated that they had no previous knowledge of HPV. One-third of them (215) knew of HPV, and two women 0.3%) did not answer this question. When asked if HPV is a responsible factor for cervical cancer, only 27.6% (or 178) confirmed that they knew this; 7.6% responded “no,” and most of them (64.7% or 417) had no knowledge of this issue. Of the 645 women involved in our study, only 29.6% (or 191) had previously heard of the HPV vaccine, 70.1% had no prior information about the HPV vaccine, and only 0.3% did not answer the question  and compared to those that were informed about vaccination by doctors  or via the internet   do not know or think it is not true that HPV is a factor responsible for the development of cervical cancer. Other studies have showed similar results, such as a study in Nigeria , whereasTwo-thirds of Kosovo women stated that they had never heard about the HPV vaccine, and only 29.6% of them have some information about the HPV vaccine. The percentage of women that know that the HPV vaccine can prevent the development of cervical cancer is even lower (24%). These results are far lower than the rates reported in studies conducted in other countries , 21, 22.Women with higher education and younger in age, have more access to the proper information, as a result of easier access to updated information from the media, internet or literature, increased awareness and regular consultations with doctors, therefore they are more keen to understand the importance of HPV infection and its relationship to cervical cancer, as well as HPV vaccination as the most important measure to prevent cervical cancer.This study has some limitations. As a cross-sectional study, it may exclude causal relationships between various factors and results. Also, because the information was collected through questionnaires, there is a possibility of incorrect answers, which could lead to possible bias. Despite these possible limitations, the study had quite a high rate of response. Information was gathered from a large number of participants, making it a very representative sample.Based on our results, the level of knowledge and awareness of HPV infection, the HPV vaccine, and its causal association with cervical cancer is generally very low among Kosovo women. Also, it can be concluded that the level of vaccination against HPV in Kosovo is extremely low. The results also indicate that having a higher level of education, living in urban areas, and being younger are favorable factors for having more information about HPV infection and the HPV vaccine.Based on our study data, there is an immediate need for the development of a proper educational program about HPV infection and the importance of HPV vaccination as a preventative measure against the development of cervical cancer.Additional file 1. Questionnaire.


In 2012, there were 2,454 cases and 1,676 deaths from cervical cancer in Kenya. Human Papilloma Virus (HPV) is responsible for 99% of all cervical cancers. National cervical cancer prevention guidelines recommend HPV vaccination among HPV-naïve pre-adolescent girls' prior to onset of sexual activity preferably through school-based interventions. Similarly, Voluntary Male Medical Circumcision (VMMC) programs also reduce sexually transmitted infections like HIV, and ideally should also be conducted prior to the onset of sexual activity. The Families Matter! Program (FMP) is a school-based evidence-based HIV prevention intervention for parents and guardians of pre-adolescents aimed to enhance protective parenting practices in order to reduced sexual risk-taking among adolescents. In this paper we describe how we will recruit a cohort of 55 parent-child dyads in a primary school in Kisumu County then implement and evaluate an adapted FMP program that incorporates VMMC promotion and HPV vaccination in conjunction. It is anticipated that the intervention will enhance parental-child communication about sexual matters, promote safe sexual practices and uptake of biomedical prevention interventions and overall reproductive health among the pre-adolescents Cervical cancer contributed to 21% of the cancer cases among women.3 In Kenya in 2012, there were 2,454 cases of cervical cancer cases, 1,676 cancer deaths and a cervical cancer screening coverage rate of 3.2% among women aged 18-69 years.5 Human Papilloma Virus (HPV) is responsible for 99% of all cervical cancers. HPV subtypes 16 and 18 cause up to 70% of all cancers.1 Human Immunodeficiency Virus (HIV) is postulated to facilitate the progression of HPV infection to cervical cancer.6 The prevalence of cervical cancer is therefore unsurprisingly highest in developing countries which also bear the burden of HIV.7Cervical cancer is the second most common cancer in women living in resource limited settings. There were approximately 445 000 new cases in 2012 in resource limited settings contributing to 84% of the new cases worldwide. In 2012, approximately 270 000 women died from cervical cancer; more than 85% of these deaths occurring in low- and middle-income countries.8 Whilst awareness of cervical cancer has been shown to promote uptake of HPV vaccine, 9 barriers exist, and studies suggest that some Kenyan parents of adolescent children fear that that administration of an HPV vaccine could encourage their daughters to have sex. Published literature documents HPV vaccine uptake of 31% and completion of 70%.9 Furthermore, the HPV vaccine is not yet available in routine clinical care in Kenya.Cervical cancer can be prevented through HPV vaccination among pre-pubescent girls. The Kenya cervical cancer prevention guidelines recommend the administration of HPV vaccine to pre/early adolescent prior to onset of sexual activity. This should preferably be done through a school-based program targeting girls in primary school from classes 4-8, corresponding to an age range of 9 to 13 years. The rationale for this age group is that they are HPV-naïve and will have the highest antibody response to the vaccine.11 The Kenya Voluntary Male Medical Circumcision (VMMC) strategy (2014/5-2018), aims to reduce new HIV infections by increasing the proportion of men aged 15-49 that are circumcised to 80%. For the greatest effect in preventing HIV acquisition, MC should be performed prior to the onset of sexual activity.12 Published literature documents a VMMC up-take of 71% through school-based programs.13 In Kenya sexual activity has been documented to begin early, prior to 15 years of age.14 As such, school based interventions have been widely implemented to reach large numbers of adolescents with HIV and SRH messages.15Male Circumcision (MC) has also been shown to have a protective effect against Sexually Transmitted Infections (STIs) like HPV and HIV. Male circumcision (MC) reduces the risk of STI and HIV acquisition in men by 35% and 60% respectively.18 FMP retention rates of 90% have been documented.17 During implementation, Kenyan parents reported having felt ill-equipped to discuss sexual matters with their children.16Families Matter! Program (hereafter referred to as FMP) is an evidence-based HIV prevention intervention for parents and guardians of adolescents aged 9-12 years. The exclamation is placed to emphasise the importance of the families in helping adolescents avoid risky behaviour such as early sexual activity and drug abuse. FMP aims to enhance protective parenting practices that are associated with reduced sexual risk-taking among adolescents and promote parent-child communication about sexuality and risk reduction. FMP provides education on HIV prevention, STI risk reduction and contraception. Families Matter! Program was modified to the Kenyan context from the US-based Parents Matter! Program in 2003-2004. Following its implementation, the programme was evaluated and shown to be acceptable and also retained its effectiveness in promoting parental skills, parent-child communication and adolescent sexual risk reduction.the social learning theory, to encourage parents to provide supportive environments, reinforce competencies, supervise their children and reduce contact with poor role models. Secondly the problem behaviour theory to bolster children's competencies, promote positive behaviour and reduce opportunities to engage in risk behaviour. Thirdly the theory of reasoned action equips parents with skills to communicate their own attitudes and norms to their adolescents to modify the adolescent's behaviour. Finally, the social cognitive theory enhances parents' efficacy in their ability to communicate with their children about sexual topics. 19FMP's theoretical framework is guided by four theories. Firstly 17 We propose to provide an adapted FMP program that incorporates VMMC promotion as a component of HIV prevention and HPV vaccination as a component of STI risk reduction among parents/guardians at one public primary school within Kisumu County to enhance HPV prevention. In this paper we describe our methods that we propose to undertake and specific aims we intend to achieve in order to assess the feasibility of implementing an adapted FMP in the Kenyan setting.Nationally interventions to provide HPV vaccination, VMMC and family education are currently provided in isolation.20 Kisumu County was chosen based on its high HIV prevalence (16% vs. 5% country wide),21 the highest proportion of young persons whose age of sexual debut was before 15 years (21% vs. 12%) and the highest prevalence of STIs (3% vs. 2%) among sexually active persons in the reproductive age group.21 Day primary schools provide a suitable target population of children in classes' 4-8 from which to draw children who are in daily contact with their parents to enhance parent-child communication.18We will conduct a cohort study among parent-child dyads within one public primary day school in Kisumu County.18 HPV vaccination 9-13 years, 8 VMMC 10-14 years,15 all of which are best delivered before the onset of sexual activities.14 The parents must give informed consent, commit to attending all six FMP sessions, bring their child to the 5th session and participate in ‘home assignments’.18 Only one eligible child per household will be included in the study. Pre/early adolescent boys that have already undergone VMMC (and subsequently their parents)will be ineligible for inclusion. Similarly, pre/early-adolescent girls that have already received HPV vaccination will also be excluded . Where either parental consent or assent from the pre/early-adolescent cannot be obtained, the parent-child dyad will be ineligible for inclusion.The study population will be comprised of parents of at least one pre/early-adolescent male or female child (aged 9-12 years) in day schools. The age range chosen is ideal for each of the three programs i.e. FMP 9-12 years,To design the evaluation study, we developed a series of specific aims and corresponding hypotheses:To determine the uptake and completion rate of HPV vaccine and associated parent and child characteristics among pre/early-adolescent girls who participated in an adapted school-based FMPWe hypothesize that promotion of HPV vaccine uptake through FMP will double vaccine uptake from 31% to 62% while maintaining the same completion rates of 71%To determine the uptake of VMMC and associated parent and child characteristics among pre-adolescent boys who participated in a school-based FMPWe hypothesize that FMP will attain a VMMC uptake of 80% from the inception of the program to the 6 months booster sessionTo document lessons learnt during the promotion of HPV vaccination for pre/early-adolescent girls and VMMC for pre/early-adolescent boys through a school-based FMP.We hypothesize that the program will provide valuable lessons as to the feasibility and outcome of promotion of HPV vaccine uptake and VMMC through a school-based FMP program9 and VMMC uptake of 71% through school based programs 13 as well as and FMP retention rates of 90% 17 documented in the literature. Using HPV vaccine uptake (in order to obtain the largest sample size22), and sample size formula for calculation of difference in proportions, to double HPV vaccine uptake (from 31% to 62%) with a significance level of 5% and power of 90% would require a sample size of 50.23We based our subsequent sample size computation on HPV vaccine uptake of 31% and completion of 70% 20 Given the FMP recommends groups of 12-18 participants, we will recruit four groups of approximately 15 parent-child dyads. To improve retention rates, we will provide transport reimbursement and refreshments during sessions. Although absenteeism will be discouraged, makeup sessions will be given for parents who miss a session and are willing to continue with other sessions. We will attempt to make-up for missed sessions by having parents attend make-up sessions in alternate groups as this can affect group dynamics.18To adjust for an attrition rate of 10%, a total of 55 dyads will be recruited to participate.18 will be adapted to include information on VMMC15 and HPV vaccination8 that is currently found in different HIV program guidelines by a team of health program managers and certified FMP providers.The current FMP curriculum15 The County Health Promotion Officers  who will be involved in the study will notify the County Education Officers who will in turn get in touch with the School heads of the potentially participating schools. Once a school is finally chosen, the study team will make an inception visit to plan study implementation with the school head. We will also involve the head of the participating health facility to ensure that the facility is equipped to implement study proceduresThe County Health Management Team (CHMT) will be contacted to obtain approval to conduct the study. We will adapt the methods used by a school-based VMMC program in the former Nyanza province when conducting school-based VMMC projects.During a Parents-Teachers meeting, a study team member will make a short presentation about the study. Interested parents/guardians will be asked to provide their names and contact details. Interested parents will be contacted at a later date and informed of the study procedures. Those that are willing to participate will be invited to the study's first formal meeting at the school grounds  where study procedures will be presented in detail and written consent obtained from those willing to consent to participate in study procedures.18This will be delivered by a certified FMP trainer through six 2-hours' sessions; five sessions will be administered over a 5-week period and the 6th will be conducted six months after the 5th session. The first 5 sessions will involve (i) getting to know you and understand your child, (ii) effective parenting, (iii) parents' role in sexuality education; the information in this session will also include HPV vaccination and MC for HPV prevention, (iv) how to increase your comfort and skills in discussing sexuality issues and (v) discussing sexuality and handling peer pressure. In the 6th session, (vi) a booster session will be done to review the FMP. This will be done with parents who participated in the school health program whether or not they accepted to vaccinate their daughters or allow their sons to undergo VMMC. Minutes of each of the meetings will be documented for analysis.Vaccine administration and VMMC services will be availed for free at a selected public health facility for a 7 months' period from the beginning of FMP implementation. The pre/early -adolescents that undergo any procedures at the selected facility will be linked to the study by the use of study-specific referral forms and unique study-specific identifiers.Parental-child dyads will be assigned dyad-specific interlinked participant identifiers. E.g. if a parent is FMP-1-0; his or her child will be identified as FMP-1-1. Our study will therefore be able to link parent and child information to uptake. The same identifiers will be noted on the vouchers which participants will be requested to present to a selected health facility should they take up the VMMC/HPV vaccination interventions. Data will be collected from parents and their pre/early adolescent children separately using, paper or electronic data collection tools.24Data from parents/guardians will include demographic information i.e. age, sex, relationship to the child, education level, marital status, occupation, number and ages of other children, communication with their children about sexual matters, knowledge about HIV and cervical cancer, participation in cervical cancer screening programs for females and VMMC programs from males, whether they are from a traditionally-circumcising or non-circumcising community, etc. Data from the adolescents will include demographic information, e.g. age, sex, education level, knowledge on HIV prevention and source of that knowledge, communication with their parent about sexual matters, etc. Data will be collected at baseline (prior to the 1st session) and after completion of the 5th session. During each session, anonymised deliberations will be documented and analysed to document experiences of the participants. Data will be entered into an MS Access Database and uploaded into SAS 9.2 for analysis.20 All assumptions regarding type, independence, normality and variance of the data will be tested.25 Thematic content analysis will be used to identify emerging themes and document barriers and facilitators to promoting HPV vaccination and VMMC through FMP from project documents, deliberations of the sessions and study team members' experiences.26Measures of central tendency and proportions will be used to summarise characteristics of parent child-dyads. One parent-child dyad will be considered as one unit. HPV vaccine up-take will be described as the proportion of eligible adolescent girls who received the HPV vaccination during the study period. Among those who received the initial dose of HPV vaccine, HPV completion will be described as having received all the 3 doses of HPV. Logistic regression will be used to describe parental and child characteristics associated with HPV vaccine uptake and completion. VMMC uptake will be described as the proportion of eligible pre/early-adolescent boys who underwent VMMC during the study period. Logistic regression will be used to describe parental and child characteristics associated with VMMC uptake.18 HPV vaccination is also given over a 6 months' period.8 Moreover, HPV and VMMC services will be available for free at selected public health facilities for a 7 months period from the beginning of the FMP sessions. The study timeline is shown in This will take into consideration the length of the FMP program, i.e., 5 weeks for implementing the intervention and a booster session 6 months later.Written informed consent will be obtained from parents/guardians of the participants and assent from the minors. The informed consent process will be administered in the language the participants and guardians feels most comfortable, in English, Kiswahili or Dholuo. They will also be informed of the referral procedures as described in the intervention. A detailed description of all procedures including period of study will be provided.No personal identifiers will be collected and all collected information shall remain private. All data collected will be kept secured, in locked storage spaces or in password-protected files and computers for the digital files. Furthermore, all staff will be trained in ethical procedures and measures to protect confidentiality; they will also be required to sign confidentiality agreements. Ethical approval for the conduct of this study will be sought and obtained from the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) Ethics Review Committee that cater for research projects in Kisumu County. Study approval will only commence following liaison and approval with the County government of Kisumu, officials from the ministry of education and the heads of the participating school and health facility.Study findings will be disseminated internally to participants in a debrief session, staff of the participating schools, county government officials and externally in national stakeholder forums, international conferences and in peer-reviewed publications.27It is anticipated that the intervention will enhance parental-child communication about sexual matters, promote safe sexual practices and overall reproductive health among the pre/early-adolescents and the uptake of biomedical HIV and HPV prevention interventions.


Plasmodium has evolved to regulate the levels and oxidative states of iron protoporphyrin IX (Fe-PPIX). Antimalarial endoperoxides such as 1,2,4-trioxane artemisinin and 1,2,4-trioxolane arterolane undergo a bioreductive activation step mediated by heme (FeII-PPIX) but not by hematin (FeIII-PPIX), leading to the generation of a radical species. This can alkylate proteins vital for parasite survival and alkylate heme into hematin–drug adducts. Heme alkylation is abundant and accompanied by interconversion from the ferrous to the ferric state, which may induce an imbalance in the iron redox homeostasis. In addition to this, hematin–artemisinin adducts antagonize the spontaneous biomineralization of hematin into hemozoin crystals, differing strikingly from artemisinins, which do not directly suppress hematin biomineralization. These hematin–drug adducts, despite being devoid of the peroxide bond required for radical-induced alkylation, are powerful antiplasmodial agents. This review addresses our current understanding of Fe-PPIX as a bioreductive activator and molecular target. A compelling pharmacological model is that by alkylating heme, endoperoxide drugs can cause an imbalance in the iron homeostasis and that the hematin–drug adducts formed have strong cytocidal effects by possibly reproducing some of the toxifying effects of free Fe-PPIX. The antiplasmodial phenotype and the mode of action of hematin–drug adducts open new possibilities for reconciliating the mechanism of endoperoxide drugs and for malaria intervention. II-PPIX). From a simple reactant and cofactor often used in biological assays ,4522,45]One notable example of how Fe-PPIXs can play distinct roles is the fact that not only does ferrous heme not spontaneously dimerize into β-hematin crystal, but it actually suppresses crystal formation when assayed under low molecular oxygen. One plausible explanation for this is that heme binds to hematin through μ-oxo-dimeric speciation, which antagonizes the head-to-tail dimer required for the formation of β-hematin crystals. As heme antagonizes hematin, this constitutes a proof-of-concept that antioxidant treatment by chemically reducing ferric hematin into ferrous heme can kill parasites, albeit not in a drug concentration range that is usable therapeutically .II-PPIX) and the tin protoporphyrin (SnIV-PPIX), can also bind to soluble hematin and inhibit β-hematin crystal formation while also being adsorbed on growing crystal surfaces and suppressing their elongation [IV-PPIX is five times more potent as a β-hematin inhibitor than its counterpart ZnII-PPIX [IV-PPIX and FeII-PPIX are potent β-hematin inhibitors and coincidently contain metals with two main oxidation states  whereas zinc is redox-inactive. Supporting this observation, it was recently demonstrated that the antiplasmodial activity of the redox-active FeIII-PPIX is abrogated by pre-exposure to the antioxidant (N-acetyl-cysteine), but the same abrogation was not observed for the redox-inactive Zn-PPIX [Plasmodium redox homeostasis.Similar to heme, other protoporphyrins IX (PPIX), such as the zinc protoporphyrin  were able to block β-hematin formation . This fiP. falciparum asexual blood stages, being as potent as artesunate or artemisinin. For instance, the fifty percent inhibitory concentration (IC50) value for hematin is 24,000 ± 4000 nM [50 values for hematin–drug adducts can be as low as 10 nM. Finally, these authors demonstrated by mass spectroscopy analysis that the hematin–drug adducts but not their parent drugs (artesunate or artemisinin) were bound to Hz isolated from parasite samples, suggesting that the observed β-hematin inhibition using cell-free conditions translated into a blockade of Plasmodium heme detoxification in a cell culture  redox chemistry between heme and peroxide drugs is mandatory and conserved for all drugs; (ii) redox chemistry is present in all three stages of the asexual blood life cycle ; (iii) the resulting hematin–drug adducts can bind to hematin and inhibit β-hematin crystal formation.Inside the DV, heme detoxification is centered on the conversion of soluble hematin into an insoluble head-to-tail hematin dimer; in other words, it is centered on suppressing soluble Fe-PPIX species. Outside the DV, a et al.  providedDespite all this, a persistent question was whether antimalarial endoperoxides display β-hematin inhibitory activity when ferrous heme is employed as a starting reactant, reproducing a cellular environment in which a peroxide drug encounters heme and further proceeds in the heme detoxification process to suppress Hz formation. Recently, Ribbiso et al.  addresseRegarding the three steps involved in the formation of β-hematin crystals when assayed using ferrous heme—i.e., oxidation of heme into hematin, hematin dimerization, and crystal formation—the findings indicate that when endoperoxides undergo hematin–drug adduct formation, they have an inhibitory effect on all three steps of hematin biomineralization. Firstly, adduct formation itself consumes heme, which would naturally be converted into hematin . Secondl50 values for the β-hematin inhibitory activity assayed on ferrous heme, although dihydroartemisinin was found to be a more potent antimalarial agent than artemether or artesunate [By correlating the compelling findings of Ribbiso et al.  and Ma etesunate . A similtesunate ,68. For tesunate ,70,71. Ftesunate . Artesuntesunate ,73,74P. falciparum with potency comparable to parental drugs [The main hypothesis proposed for the antimalarial activity of peroxides is the radical-induced alkylation of client molecules . These mal drugs  can be iPlasmodium parasites?Unlike the parent peroxides, the ability of hematin–drug adducts to alkylate molecules is jeopardized, especially considering that the peroxide bond is no longer available to participate in the Fenton reaction, which is needed for radical formation. The structural necessity of the endoperoxide bond for artemisinin to display antimalarial activity has been directly assessed by multiple studies from different research groups ,77. FurtPlasmodium heme detoxification. It is also possible that these hematin–drug adducts, viewed as modified Fe-PPIX, may reproduce the toxic role of free Fe-PPIX in killing parasites, as typically observed in parasites treated with classic heme detoxification suppressors such as chloroquine and amodiaquine [As mentioned above, the two main hallmarks of heme detoxification suppression are the augmentation of free Fe-PPIX levels and the reduction of the Hz content. Compelling studies have showed that hematin–drug adducts inhibit β-hematin growth and Hz formation ,41,65; hdiaquine . Figure A full understanding of the cellular distribution and accumulation of hematin–drug adducts remains an unmet challenge; as such, identifying these characteristics could provide a model to explain the scope and limitation of this class of potential antimalarial therapeutics. Via this reasoning, the parasite cytosol is enriched in reductants such as glutathione . This kiPlasmodium biology: redox homeostasis and heme detoxification. Integrating the concepts of how antimalarial peroxides can interfere in these processes is of pivotal importance. Despite the progress made, as revised above, there still questions to be answered before a pharmacological model can be developed that is capable of reconciling most of these processes.Elucidating the action mechanisms of antimalarial drugs could accelerate the development of new and effective malaria therapies. Several studies have emphasized the essential nature of the relationship between peroxide drugs and heme. It is now clear that this relationship has deep ties with the two main aspects of Plasmodium heme detoxification. For instance, the cellular concentration of the biogenic hematin-dihydroartemisinin adduct in P. falciparum can range from 1000 to a 25,000 nM depending on the parasite stage in a P. falciparum culture treated with a dihydroartemisinin bolus of 5000 nM [Plasmodium heme detoxification are less pronounced than those of chloroquine treatment.One outstanding question is why antimalarial endoperoxides, such as artemisinin, do not potently inhibit the  5000 nM . This co 5000 nM  to demonA second riddle is this: if an antimalarial peroxide alkylates heme by forming species that have a high affinity for binding to hematin and thus are highly effective in suppressing heme detoxification, a peroxide drug would be expected to exhibit appreciable accumulation inside the DV in order to get in closer proximity to the client molecule. Early studies have indicated that artemisinin and its chemical variants conjugated with fluorescent tags accumulate in the cytosol and to a lesser extent, in the DV ,82. HowePlasmodium, where direct evidence of the bioreductive activation of artemisinins by heme was observed. For the parasites in the sexual (gametocytes) and the hepatic (sporozoites) stages, the real extent of this bioreductive activation remains elusive. This is because currently there is no direct evidence of bioreductive activation for these parasites. It is known that these parasites have heme, which is supplied by de novo biosynthesis [50 values in a low nanomolar range; this contrasts with mature gametocytes, which are approximately two hundred times less susceptible to dihydroartemisinin treatment [Finally, it is important to place the pharmacological models in ynthesis ,55,56. Pynthesis ,86. For reatment . This isreatment , resemblreatment . ClearlyPlasmodium operates a synchronized system to mitigate a free flow of Fe-PPIXs across the DV membrane. Multiple studies indicate that antimalarial endoperoxides, such as 1,2,4-trioxane artemisinin and 1,2,4-trioxolane arterolane, operate a mechanism of radical-induced alkylation mediated by heme. A plethora of molecules can be alkylated, and a plausible pharmacological model is that the antimalarial activity of endoperoxides can be achieved by alkylating heme as well. In support of this notion is the fact that hematin–drug adducts are highly abundant, strong antimalarials, and potent antagonists of hematin biomineralization. These alkylated heme species recognize soluble and insoluble hematin pools, but as modified Fe-PPIX species, they do not mineralize into Hz crystals but, rather, block hematin biomineralization. Furthermore, heme alkylation alters the heme/hematin ratio and can thereby induce an imbalance in the redox homeostasis of iron species.Similar to other metalloporphyrins, hematin–artemisinin adducts bind irreversibly to growing β-hematin crystals, and this initiates the suppression of heme detoxification. These adducts act as a modified Fe-PPIX structure containing two pharmacophores: Fe-PPIX recognizes and inhibits β-hematin formation while the highly lipophilic sesquiterpene lactone from artemisinin contributes to overcome the poor lipophilicity of metalloporphyrin, in addition to its plausible interaction with parasite targets. Via this reasoning, hematin–artemisinin adducts could be seen as being heterobivalent with respect to their recognition of multiple molecular targets. Heterobivalency is one of the principles of the molecular hybridization approach for designing hybrid-based drugs , which r


The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees.This retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load.P = 0.026), CIN 2 , CIN 3 , and cervical cancer .Finally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164–10.941, Among women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions. Cervical cancer is the fourth major malignant tumor in women worldwide . In 2018Human papillomavirus (HPV) infection can lead to cervical precancerous lesions and cervical cancer . Active Therefore, the objective of this study was to investigate the changes in high-risk HPV viral load in patients with different degrees of cervical lesions to clarify the correlation between the viral load of HPV and cervical lesions and to explore the clinical value of high-risk HPV viral load for the predictive diagnosis of cervical cancer.This retrospective study included patients who first visited the Gynecology Clinic of the Second Affiliated Hospital of Kunming Medical University between January 2015 and June 2018. All methods were performed in accordance with the Declaration of Helsinki and the relevant guidelines and regulations. This study was approved by the ethics committee of the Second Affiliated Hospital of Kunming Medical University. As a retrospective study, informed consent was exempted by the ethics committee of the Second Affiliated Hospital of Kunming Medical University.The included women were women with a history of sexual activity and who spontaneously sook screening. For HPV-negative patients, re-screening for HPV in 3–5 years or anytime in the presence of symptoms was recommended. The inclusion criteria were (1) patients with positive HPV-DNA who underwent cervical cancer screening according to the latest version of the American College of Obstetricians and Gynecologists (ACOG) guidelines for cervical cancer screening and prevention practice , and (2)The age of the patients, the HPV-DNA viral load, and the pathological degree of cervical lesions at the time of screening were obtained from the clinical records. The patients were divided into five groups: normal group, CIN grade 1 group, CIN grade 2 group, CIN grade 3 group, and invasive cervical cancer group.The second generation of the Hybridized Capture II gene hybridization signal amplification system from Digene Co.  was used to detect the content of HPV-DNA in the samples. That assay can detect 13 types of high-risk HPV subtypes simultaneously. All assays were strictly performed according to the manufacturer’s instructions. The relative light units (RLUs) and positive control values (CO) of the samples were detected. The ratio of the RLU to the CO value of the positive standard was used to indicate the viral load. RLU/CO < 1.0 was considered a negative result. RLU/PC ≥ 1.0 was considered a positive result, which means that the amount of HPV-DNA per ml of sample was > 1.0 pg. According to Lorincz et al. , the virA colposcopy biopsy was performed after the diagnosis by a specialist gynecologist. The cervix, vagina, and vulva were examined at the same time. Each quadrant of the cervix was assessed. The basic principles of direct biopsy or quadrant biopsy were followed. Multi-point biopsies were taken in the vinegar white area and iodine-stained suspected lesion area and were sent directly for pathological examination. If no abnormality were found under the microscopic examination in each quadrant, samples would be taken at the squamous columnar junction or the transformation area at 3, 6, 9 and 12 o’clock of the cervix, and a sample would be taken by cervical curettage. The specimens taken by colposcopy were submitted to the pathology department of the same hospital for histopathological examination and immunohistochemistry if necessary. The final cervical pathological diagnosis was determined after quality control by two pathologists. The results were presented according to normal , CIN grade 1, CIN grade 2, CIN grade 3, and cervical cancer.t-test or ANOVA with the LSD post hoc test. Unconditional logistic regression analysis was performed for univariable and multivariable analyses to calculate the odds ratio (OR) and 95% confidence interval (CI) for the presence of cervical lesions in different viral load levels, using the normal group as the reference. P-values < 0.05 were considered statistically significant.SPSS 24.0  was used for data processing and statistical analysis. Categorical data were presented as frequencies and percentages and analyzed using the chi-square test or Fisher’s exact test, as appropriate. The continuous data were tested for normal distribution using the Kolmogorov–Smirnov test and analyzed using the Student P < 0.05)  were positive for HPV. Among them, 385 patients underwent colposcopy, and then 265 underwent cervical biopsy. Therefore, 265 patients, aged 20–73, were included in this study: 125 in the normal group, 51 in the CIN grade 1 group, 23 in the CIN grade 2 group, 46 in the CIN grade 3 group, and 20 in the cervical cancer group. The patients in the cervical cancer group were significantly older than the patients in the normal, CIN grade 1, and CIN grade 2 groups . The viral load of patients in the CIN grade 3 and cervical cancer groups was higher than that of patients in the normal group, but there were no significant differences among the other groups  had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. There were significant differences in viral load among the five pathological groups , but age was not an independent factor . For CIN grade 3, age still was not an independent factor, but a moderate load of HPV  and a high load of HPV  were independent risk factors. For cervical cancer, age was not associated, while high-load HPV  were both independent risk factors (Table Taking the normal control group as a reference, the correlations between all cervical lesions and viral load were analyzed and compared using multivariable analyses. The results showed that the viral load was an independent risk factor for the occurrence of CIN grade 1 and CIN grade 2 (CIN I: high load, OR = 3.568, 95% CI: 1.164–10.941, The correlation between HPV viral load and cervical lesions is poorly known, and the significance of HPV viral load in the detection and treatment of cervical lesions is still controversial , 18. TheIn this population, the rate of HPV positivity among the screened women was 13.5%, which is a little lower than the national rate in China . The patSince integrating the HPV DNA into the host cells is necessary for malignant transformation by the E6 and E7 proteins, the HPV DNA load has been suggested to be used as a marker of the risk of dysplasia and cervical cancer , 22. In This study has limitations. It was performed at a single center, and the sample size was relatively small, mainly because not all patients underwent Hybrid Capture II analysis. The data that could be analyzed were limited to those available in the medical charts. The exact HPV subtype was not available for many patients indicated as positive in their chart. Cytology results were not available because cytology was often performed at another lower-level hospital or clinic. No follow-up data were available. Additional studies are still necessary to refine our understanding of the relationship between HPV DNA load and cervical lesions. Since only high-risk HPV-positive patients were included, the frequency of high-risk HPV positivity in each pathological group could be analyzed.In conclusion, in the light of the previous literature, the results suggest that cervical lesions are closely related to high-risk HPV infection in women who underwent biopsy. Higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions. Therefore, high-risk HPV viral load could be used as a marker of the risk of finding high-grade cervical lesions at biopsy.


ABSTRACT IMPACT: We hosted the Indiana Clinical and Translational Sciences Annual meeting virtually this year which resulted in positive feedback survey scores over 90% and an estimated 87% cost savings OBJECTIVES/GOALS: COVID-19 has forced many in-person meetings to become virtual, not unlike our 2020 Indiana Clinical and Translational Sciences Institute Annual Meeting. However, where anecdotal feedback has shown dissatisfaction with some on-line meetings, we were able to exceed our goals of engaging our audience, securing positive feedback and even saving money. METHODS/STUDY POPULATION: More than 500 people attended the virtual 2020 Indiana Clinical and Translational Sciences Institute (CTSI) Annual Meeting on September 11. The event had two plenary speakers and was completely online, utilizing both Zoom and Microsoft Teams to connect participants with the presenters. Brian Druker, MD, director of the Knight Cancer Institute at Oregon Health & Science University, was the winner of this year’s August M. Watanabe Prize in Translational Research. He gave the first plenary presentation titled, ‘Imatinib as a Paradigm of Targeted Cancer Therapies.’ Consuelo Wilkins, MD, Vice President for Health Equity at Vanderbilt University Medical Center, gave the second plenary titled, ‘Confronting Racial Inequities through Research.' Concurrent online breakout rooms hosted the live poster session. RESULTS/ANTICIPATED RESULTS: Despite being conducted online, the virtual Indiana CTSI annual meeting registered more participants than in years past and secured high feedback scores of 90%, all while experiencing 87% cost savings over last year’s in-person meeting. By utilizing Microsoft Teams as a technology for attendees to the meeting to 'chat’ and 'network’ with one another during the poster presentations and virtual lunch break we were able to demonstrate the implementation of translational science through online plenary and general session presentations as well as the poster presentations. Mailing certificates to the poster winners in advance, allowed them to share their accolades with the audience by holding up their certificates once their winning posters were announced. An e-annual report also supported the success of the meeting. DISCUSSION/SIGNIFICANCE OF FINDINGS: The cost savings and traditionally high feedback scores received through this year’s Indiana CTSI annual meeting, mean virtual meetings are a viable way to disseminate and implement translational science. In addition the 2020 Indiana CTSI annual report received a Gold MarComm award, providing third party recognition of its impact.