Psychotherapy manuals are critical to the dissemination of psychotherapy treatments. Psychotherapy manuals typically serve several purposes, including, but not limited to, establishing new psychotherapy treatments, training providers, disseminating treatments to those who deliver them, and providing guidelines to deliver treatments with fidelity. Yet, the proliferation of psychotherapy manuals has not been well-understood, and no work has aimed to assess or review the existing landscape of psychotherapy manuals. Little is known about the breadth, scope, and foci of extant psychotherapy manuals.This scoping review aims to identify and explore the landscape of existing book-based psychotherapy manuals. This review aims to specify the defining characteristics  of existing book-based psychotherapy manuals. Further, this review will demonstrate how this information, and psychotherapy manuals more broadly, has changed over time. This project aims to make a novel contribution that will have critical implications for current methods of developing, aggregating, synthesizing, and translating knowledge about psychotherapeutic treatments.This scoping review will review book-based psychotherapy manuals published from 1950 to 2022.This scoping review will be informed by guidance from the Joanna Briggs Institute Scoping Review Methodology Group and prior scoping reviews. Traditional search and application programming interface–based search methods will be used with search terms defined a priori to identify relevant results using 3 large book databases: Google Books, WorldCat, and PsycINFO. This review will leverage machine learning methods to enhance and expedite the screening process. Primary screening of results will be conducted by at least 2 authors. Data will be extracted and double-coded by research assistants using an iteratively defined codebook.The search process produced 78,600 results, which were then iteratively deduplicated. Following deduplication, 50,583 results remained. The scoping review is expected to identify common elements of psychotherapy manuals, establish how the foci and content of manuals have changed over time, and illustrate coverage and gaps in the landscape of psychotherapy manuals. Results from this scoping review will be critical for future work focused on developing, aggregating, synthesizing, and disseminating knowledge about psychotherapeutic treatments.This review will provide knowledge about the vast landscape of psychotherapy manuals that exist. Findings from this study will inform future efforts to develop, aggregate, synthesize, and translate knowledge about psychotherapeutic treatments.DERR1-10.2196/47708 The Interpretation of Dreams in 1899. However, the origins of the psychotherapy manual are unclear, and what qualifies as the first psychotherapy manual has not been well-established. Previous work has endorsed different publications as the first psychotherapy manual, including Wolpe’s [Psychotherapy by Reciprocal Inhibition, Kelerman and Neu’s [Interpersonal Approach to Treating Depression, Paul’s [Insight vs. Desensitization in Psychotherapy, and Beck’s [Cognitive Therapy for Depression. Though the origins of manuals are not well-understood, psychotherapy manuals have evolved to play an important and prominent role in clinical research, education, and practice.Psychologists have long disseminated therapeutic knowledge and procedures through writings such as books and papers. For example, Freud first published nd Neu’s  1973  or authors. Multiple rounds of deduplication were performed. First, deduplication by URL was performed to ensure that equivalent results from the same source were removed. Next, deduplication by ISBN identifiers was performed to ensure that duplicate results based on ISBN-10 or ISBN-13 numbers were removed. Finally, deduplication by a combination of title, description, AND year was performed, as well as a combination of title, author, AND year. Manual deduplication will be conducted throughout the later review phases, if necessary. Citations will be managed in reference management software.Inclusion criteria were developed by study authors and subject matter librarians. First, manuals must be in the English language. Second, manuals must be a published book as this review focuses on books , rather than other publication forms . Third, manuals must have been published between 1950 and 2022, as this reflects a broad time period that includes the creation of a vast majority of modern psychotherapies . Additionally, this encompasses the time period in which previously identified “first” manuals were published . Fourth,Screening of book descriptions and titles will be conducted in Rayyan (Rayyan Systems) . Due to Screening fidelity  will be met through multiple rounds of test screening across the screening team and AZ. Results that will be screened by the screening team will receive 2 decisions, 1 made by KW and 1 made by another author. Screening decisions will be made on the basis of information provided . All disagreements will be resolved through consensus discussions between screeners for each result in conflict.A codebook will be devised by input from all authors. An initial codebook will be created by KW and AZ. Feedback on the codebook will be solicited from the screening team to ensure that codes reflect relevant and extractable information from results. Additionally, the codebook will be further iteratively defined through the test coding process, with additional codes proposed, discussed, and agreed upon by the coding team, KW, and AZ. Coding will be performed for all included manuals. Fidelity will be established through 3 rounds of test coding prior to the beginning of coding. The coding team will code each result based on the information provided through bibliometric information  as well as open-access information such as scholarly book reviews, freely available published portions of the book, and information provided via official sellers . Information outside of bibliometric data will be used when coding cannot be adequately performed on the information provided. Scholarly databases will be used to search book reviews when more information is necessary for coding purposes. Code disagreements will be addressed through consensus discussion or adjudication of disagreements by KW.The initial codebook includes bibliometric information , edition number, clinical target, clinical population, treatment name, treatment orientation, treatment notes, mental health provider target, treatment delivery setting, type of treatment , age of treatment target, as well as dichotomous codes for several potential adaptations to treatment based on gender identity, race or ethnicity, culture, physical illness or disability, religion, employment or role, and other adaptations that are not covered by previous categories.This scoping review is currently being conducted. Initial search across all sources was completed in July 2022. The search process produced 78,600 results, which were then iteratively deduplicated. Following deduplication, 50,583 results remained. Nearly 14.2% of results (n=7171) have been screened. A portion of included results (n=775) have been coded. Full results from this review will be submitted for publication in peer-reviewed journals.The proposed review will be the first to synthesize information about the existing landscape of psychotherapy manuals with the goal of addressing critical and unanswered questions. More specifically, we aim to identify the features of existing manuals , illuminate the ways in which psychotherapy manuals have evolved over time, and highlight current resource allocation and gaps evidenced by existing manuals. The findings from this review will be critical for future efforts to develop, aggregate, synthesize, and translate knowledge about psychotherapeutic treatments.Prior work that has focused on reviewing psychotherapy manuals has been narrowly limited to a specific treatment type, treatment focus  , or manuThere are several limitations to this work. Psychotherapy manuals can be disseminated through myriad forms and methods. Because of the disparities in how psychotherapy manuals are published and disseminated, the ability to systematically aggregate all knowledge related to this topic is arguably impossible. Therefore, we limited the search strategy to books to capture the predominant method by which manuals are disseminated. This will exclude psychotherapy manuals disseminated through peer-reviewed papers and gray literature, for example.Certain books used as psychotherapy manuals may not meet our inclusion criteria. For example, providers have previously used client-facing  books as psychotherapy manuals, yet these resources will be excluded from this review. This was decided by the authors to limit the inclusion of materials that are not focused on providing instruction to mental health professionals about treatments and treatment delivery. Additionally, providers may use other types of books or resources to inform their clinical practice that do not focus directly on delivery of an intervention . While these resources may be beneficial to delivery of psychotherapeutic treatments, they do not focus on instructing mental health professionals on how to deliver treatment.Given the history of psychotherapy manuals and psychotherapy more generally, this scoping review aims to be informed by the changing definitions and ontologies in psychotherapy research. However, it is likely that through this scoping review, a modern qualitative coding may not encompass the changing definitions of psychotherapy treatments and the language used to describe them. Coding will be performed based on the bibliometric data, which is inherently reflective of the contemporary definitions in which a manual was produced. For example, the changing understanding of “behaviorism” and “behavioral treatments,” as well as what constitutes “cognitive therapy” then versus now, may not be completely understood through the results from this review.It is possible that the databases used within this review may not have a comprehensive list of psychotherapy manuals; however, the selected databases have extensive and growing catalogs -26. DataNotably, this review will have numerous strengths. Although this is a scoping review, significant efforts will be taken to ensure that a wide variety of manuals will be included, increasing the potential representativeness of the results. Further, the use of these novel methods within this review will expand upon the growing literature on the use of machine learning to enhance reviews . Most im


Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers.The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson’s biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age ( Human papillomaviruses (HPVs) constitute a family composed of more than 150 genotypes capable of infecting both cutaneous and mucosal epithelium . For thiIn general, the likelihood of acquiring an HPV infection is highest in the age group ranging from 20 to 24 years (27.4%) and gradually decreases with increasing age, stabilizing around 19% among those aged 50 to 59 years . AdditioCurrently, the impact of multiple infections on the risk of cervical lesions is debated, as are their occurrence by chance or as a consequence of various interactions and risk factors, including age, smoking, sexual habits, and immunosuppression ,12,13. SIn ecology, biological diversity expresses the variety within an ecosystem and is characterized by two parameters, namely “richness”, which is the number of different species in the same sample, and “evenness”, which measures the relative abundance of individual species within the same ecosystem ,28. In tAll women attending the Colposcopy Unit at the Preventive Gynecology Unit of the European Institute of Oncology IRCCS, Milan, Italy, between December 2006 and December 2014, were identified from hospital file archives and selected for cross-sectional analysis. The local institutional review board approved the study protocol . Written informed consent was obtained from all subjects prior to colposcopy or surgical treatment for the use of data for scientific purposes. Patients were included if they met the following criteria: (a) age at diagnosis of 18 years or older; (b) colposcopic-guided cervical biopsies due to abnormal Pap smear or surgical treatment for preneoplastic and neoplastic cervical lesions; (c) histological confirmation of any grade of CIN, adenocarcinoma in situ (AIS), and invasive cervical carcinoma (ICC); and (d) known HPV status. Patients were excluded if they (a) denied informed consent or (b) had unavailable HPV status. Data regarding the main clinical, laboratory, and pathological characteristics of patients were recorded in a dedicated database. All histological diagnoses were conducted on colposcopic-guided biopsies  or on surgical tissue by dedicated gynecological pathologists from the Division of Pathology at our Institute.A ThinPrep PreservCyt cervical sample  was collected from all patients to perform a Linear Array HPV Genotyping Test . The linear array test uses biotinylated PGMY09/11 consensus primers to amplify a 450 bp region of the L1 gene, detecting the following 37 HPV genotypes: HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73 (MM9), 81, 82 (MM4), 83 (MM7), 84 (MM8), IS39, and CP6108. The denatured polymerase chain reaction products were then hybridized to an array strip containing immobilized oligonucleotide probes. The results were visually interpreted by two independent operators using the provided reference guide, following the manufacturer’s protocol, and subsequently compared to reach a final conclusion.kD) is calculated according to the following formula:kjn, kN, and kS are the abundance of the j-th HPV type, the total abundance of each species, and the number of species for the k-th histologic grade, respectively. As such (1 − kD) ranges from 0 (no biodiversity) to 1 (infinite biodiversity). The histologic grade was categorized on k = 4 levels as Normal, CIN1, CIN2, and CIN3+, where CIN3+ was defined as having a CIN3 grade or AIS or ICC. Age parameters included mean, standard deviation (SD), median, and interquartile range (IQR) and were tabulated using HR and low-risk (LR) richness as well as histologic grade. The significance of the association between age and richness or the histologic grade was assessed using the Kruskal–Wallis test, and the association between richness and histologic grade was determined using the chi-square test. Empirical Simpson’s biodiversity index for single HR type infection distributions was obtained using the nonparametric bootstrap, stratified via histologic grade resampling with replacement with 10,000 replications. Bootstrap 95% confidence intervals (95% CIs) were estimated using the percentile method. HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered high-risk (HR) while all other genotypes identified through the linear array test were classified as low-risk (LR) types. All tests were two-tailed and considered significant at the 5% level. All analyses were carried out using SAS 9.4  and Stata , College Station, TX, USA, StataCorp LLC).HPV type richness is defined as the number of different genotypes per patient and is categorized as 0, 1, or ≥2. The Simpson’s biodiversity index . All subjects were unvaccinated at the baseline.The most common histologic grade was CIN3+, observed in 266 patients (56.7%), including 215 women diagnosed with CIN3, 39 with ICC, and 12 with AIS. In total, 76 patients (16.2%) did not test positive for any HR types, while 335 patients (71.4%) did not show any LR types. The most prevalent infection was a single HR type, accounting for 321 patients (68.4%), irrespective of the presence of any LR type. Two or more types were less common for both HR and LR, with 72 patients (15.4%) and 51 patients (10.9%) having multiple infections, respectively see .p = 0.007). There was no significant association between age and LR richness (p = 0.65) or age and histologic grade (p = 0.22)  was observed between both HR and LR richness and histologic grade. The richness of HR types decreased as the histologic grade increased; notably, 43.4% of patients with CIN3+ had only one HR type, compared with the lower histologic grades (see A significant association (ades see .p = 0.04) and CIN2 grades (p = 0.004) but not for CIN1 (p = 0.79) and CIN3+ (p = 0.68)  see .Empirical bootstrap distributions for single HR-type infections demonstrated that, as the histologic grade increased, the mean biodiversity index decreased. The normal and AIS grades were exceptions, with mean biodiversity indices of 1 − D = 0.85  and 1 − D = 0.79 , respectively. The mean biodiversity indices for CIN1, CIN2, CIN3, and ICC were as follows: 1 − D = 0.94 ; 1 − D = 0.85 ; 1 − D = 0.75 ; and 1 − D = 0.53 , respectively A,B.Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. Although there was considerable overlap between all clusters, the CIN1 grade exhibited the widest range in age and the lowest in biodiversity index, whereas ICC was the histologic grade with the greatest spread in biodiversity index and the lowest in age see .Specific HPV genotype frequency distribution, HPV genotype frequency distribution needle plots by histology for HR Richness, HPV genotype frequency distribution needle plots by histology for HR Richness ≥ 2, HPV genotype frequency distribution needle plots by histology for LR Richness = 1 and HPV genotype frequency distribution needle plots by histology for LR Richness ≥ 2 are detailed in The results of this study reveal a significant correlation between HR-HPV richness and the histological grade of cervical dysplasia. This association is particularly evident in squamous lesions, where there is a discernible gradient. As the histological grade of the lesion increases, biodiversity decreases. Notably, 43% of patients with CIN3+ lesions exhibited only one HR-HPV type. The principle “one virus–one lesion” aligns consistently with findings in the existing research ,30,31,32Detecting the presence of HPV in histological samples is more accurate than in cervical samples, as demonstrated by several studies in the literature. Within the landscape of existing tests, the linear array test targets L1 viral protein rather than E6/E7 oncogenes; during the oncogenic process, HR-HPV viruses may integrate their genomes into cellular DNA, and during this process, the virus can lose the L1 gene, making the test no longer capable of detecting the presence of the virus. Beyond this assumption, linear array performance has been validated by the VALGENT framework, showing similar sensitivity with higher specificity to detect CIN2+ than the Hibryd Capture 2 test, and the detection of 13 hrHPV types fulfills the clinical accuracy requirements for primary cervical cancer screening . Quint eWhen analyzing the correlation between age and HPV infection, it becomes evident that multiple genotype infections, both HR-HPV and LR-HPV, are more frequent in younger age groups. Specifically, women with multiple HR-HPV infections are, on average, four years younger than women with multiple LR-HPV infections, as shown in Significantly, we observed an association between both HR and LR richness and histologic grade. The richness of LR and HR types decreased as the histologic grade increased. This is in agreement with previous studies indicating that single HR-HPV infections become significantly more common as the cervical lesion grade worsens. Additionally, multiple genotype infections are associated with a lower risk of CIN2+ ,40. Li eIn contrast, according to Spinillo et al., multiple HR-HPV infections are associated with larger cervical lesions, especially in women infected by HPV 16 and in CIN3+ lesions. Larger lesions are linearly associated with increasing severity of CIN . Likewisp-value (p = 0.04). However, this correlation, although not statistically significant, is also apparent in the CIN3+ category. This absence of a statistically significant association can be interpreted by specifying that the CIN3+ category is highly heterogeneous, encompassing not only CIN3 but also AIS and squamous ICC.As already found by Herrero et al. , our anaNevertheless, it is now widely accepted that CIN2 represents a different category from CIN3+, which warrants distinct and individualized management. Recent Bayesian analyses have separately reported the risk of CIN2 and CIN3+ based on individual HR-HPV genotypes, supporting the concept that CIN2 is distinct in histological and biological identity from CIN3+ ,46. IndeImportantly, as the histologic grade increases, the mean biodiversity index decreases for single HR-HPV infections. The CIN1 category represents the group of lesions with the highest biodiversity index. This finding is consistent with the concept that cervical LSIL represents the clinical and morphological expression of active replicating HPV infection, without a significant risk of developing invasive neoplasia, as reiterated by the WHO classification of female genital tumors . MoreoveInterestingly, the group with AIS histology exhibited a higher biodiversity index than the high-grade squamous lesions, although still lower than the group of HPV-infected patients without histologically confirmed lesions. This finding could be attributed to the lower number of AIS cases in our study sample and the fact that glandular dysplasias originate as such, rather than progressing through degrees as in cervical squamous intraepithelial lesions. No data are available in the previous literature regarding differences in the distribution of HPV genotype richness and biodiversity index between glandular and squamous cervical dysplasias. Li et al. only reported a similar gradient in the distribution of HR-HPV genotype richness in squamous precancerous and cancerous cervical lesions, finding a significant increase in the proportion of single HPV genotype infections as the cervical lesion worsens from CIN1 to squamous ICC .Lastly, a distinct distribution of histologic grade categories was identified according to age and biodiversity index. In particular, the CIN1 grade exhibited the widest range in age and the lowest range in biodiversity index. In contrast, ICC showed the greatest variation in biodiversity index and the lowest age range. Actually, it is well recognized that CIN1 solely represents the biological expression of HPV infection and not a pretumoral lesion. Therefore, it can occur at any age. In contrast, cervical carcinoma results from persistent integrated HPV infection and a prolonged transformation process of the cervical epithelium, with the peak incidence of ICC occurring after the age of 40 years.To our knowledge, this is the first study to apply the statistical concept of biodiversity, as measured by Simpson’s index, to cervical lesions rather than the genome of HPV genotypes. The difference between our study and other work published in the literature is that we investigated the concept of biodiversity related to the presence of various HPV genotypes, both HR-HVP and LR-HPV, present in dysplastic lesions of different histological grades. This approach allowed us to investigate the role of single versus multiple infections in cervical carcinogenesis and the differences in biodiversity between squamous and glandular cervical dysplasias. The strength of our study lies in the availability of histological diagnoses performed by experienced gynecologic pathologists for all enrolled women, ensuring the reliability and reproducibility of the results. Nevertheless, limitations of this study include selection bias related to the single-center analysis, a cross-sectional study design, and a relatively small representation of multiple infections for both HR and LR types.HPV genotype richness and biodiversity of cervical dysplasias may play a fundamental role in predicting the risk of high-grade cervical lesions and allowing for the individualized management of potentially regressive precancers, especially CIN2 in young women with multiple genotype infections. However, this correlation was not demonstrated for glandular cervical dysplasias, as their origin does not follow a progressive degree pattern as seen in squamous lesions. Further longitudinal studies with larger, multicenter cohorts are needed to confirm the impact of single versus multiple genotype infections and the biodiversity index of cervical dysplasias in the development of precancerous and cancerous lesions of the cervix in the context of persistent HPV infections.


Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Neisseria gonorrhoeae (NG), and co-infections with human papillomavirus (HPV) in a hospital gynecology outpatient clinic in the Haikou region in 2021.The purpose of this study was to study the infection rates of From January to December 2021, the Women and Children Medical Center of Hainan Province collected 2389 samples of cervical exfoliated cells and vaginal swab specimens from gynecologic outpatients. The samples were then analyzed descriptively for data, and the detection rate of each pathogen was tallied. All vaginal swabs were obtained for CT, UU, and NG DNA testing, and cervical exfoliated cells for HPV genotyping. Analyses were performed on the detection rate of each group.P < 0.05).In 2389 samples, the frequencies of pathogen identification among the 2389 samples were as follows: UU (58.43%); HPV (17.29%); CT (7.99%); and NG (0.38%). HPV, CT, UU, and NG were detected in 33.33%, 22.55%, 77.45%, and 2.94% of individuals between 15 and 20 years of age, respectively. The detection rates of CT, UU, and NG were substantially greater in the HPV-positive group than the the HPV-negative group (Among gynecologic outpatients at a hospital in the Haikou area, the probability of mixed infections with genital tract pathogens in HPV-positive patients was higher compared to HPV-negative patients. Reproductive tract infections are becoming more prevalent in younger people, hence adolescent sexual health education needs improvement. Sexually transmitted infections (STIs) are a major source of morbidity globally in both men and women. The use of Pap smears and human papillomavirus (HPV) testing has led to an increase in the detection of cervical dysplasia and a decrease in the incidence of cervical cancer. Mobile health programs enhance cancer screening rates in the general population and are of enormous value in poor nations. New screening technologies, such as p16/Ki67, HPV self-testing, and the application of artificial intelligence in colposcopy evaluations, should be widely used. Focusing on pre-cancerous lesions and developing tools for women at risk for persistent and recurrent pre-cancerous lesions following primary conization , and identifying groups at high risk have clinical value .Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), and Neisseria gonorrhoeae (NG). HPV infections are linked to vaginal microenvironmental dysfunction. Compared to women without bacterial vaginosis (BV), the hrHPV infection rate in women with BV is increased , and Neisseria gonorrhoeae Test Kit [DA0063]  were used to identify the three pathogens, and all procedures were carried out in accordance with the instructions on the kit packaging. The SLAN-96P real-time fluorescence quantitative PCR apparatus was used for DNA detection .The P < 0.05.SPSS 26.0 software was used for statistical analyses. Count data are expressed as n(%). A χ2 or Fisher exact test was used to compare rates between groups, as indicated. The difference was considered statistically significant at a Among the samples tested, UU had the highest detection rate (56.84% [1358/2389]), followed by HPV (17.29% [413/2389]), CT (7.99% [191/2389]), and NG (0.38% [9/2389]).A total of 413 HPV-positive samples were detected from 2398 patients. The total HPV subtype detection rate was 16.71% (69/413); HPV subtype 52 had the highest detection rate. All 21 HPV subtypes detectable in the kit were detected. The detection rates for the top 5 HPV subtypes were as follows: 52 (69/413); 16 (56/413); 39 (38/413); 51 (38/413); and 58 (36/413).P < 0.05). The HPV, CT, UU, and NG detection rates in the 21–25 year age group was second only to the 15–20 year age group; the difference was statistically significant compared with the other age groups (P < 0.05). There were no significant differences in the HPV, CT, UU, and NG detection rates between the 26–30, 31–35, 36–40, and ≥ 41 year age groups.The results showed that the HPV, CT, UU, and NG detection rates were the highest in the 15–20 year age group; the difference was statistically significant compared with the other age groups  vs. 1035 (52.38%); P < 0.001], and NG  detection rates were significantly higher in the HPV-positive group than the HPV-negative group.The samples were separated into groups of HPV-positive and -negative patients based on the results of HPV tests. CT, UU, and NG detection in each group was recorded. CT .The findings of this study demonstrated that among patients with an HPV infection, there was a higher likelihood of detecting CT, UU, and NG in cervical samples. The pathogen identification frequencies among the 2389 samples were as follows: UU (58.43%); HPV (17.29%); CT (7.99%); and NG (0.38%). The prevalence of UU has been reported to be 20% in South America, 41.9% in Italy, and 51.5% in Africa . The higHPV is mostly spread via sexual contact, and the likelihood of infection increases with age and sexual behavior . HPV is The primary pathogens that cause infections of the female reproductive system are HPV, CT, UU, and NG. In the early stages of infection, these pathogens frequently cause no or moderate symptoms, which makes it easy to miss the diagnosis or misdiagnose the symptoms and cause recurring sickness, such as non-gonococcal urethritis, pelvic inflammation, gonorrhea, and chronic cervicitis , 22. In The probability of HPV infection is increased by polymicrobial co-infections in addition to age-related variables . CervicaCT is recognized as a significant co-factor for HPV infections . Other SThe pathogen that most often infects the female reproductive system, UU, has recently been identified as one of the major risk factors for the development of HPV infection or cervical dysplasia . When UUAlthough there were few NG-positive samples and a low incidence of NG infections in our study, we did show a higher rate of NG infections in the HPV-positive group. In addition, we showed a low rate of NG infections and a low number of NG-positive samples, but still found an increased rate of NG infections in the HPV-positive group. This finding suggests that NG infections also increase the risk of HPV infections and should be taken seriously and treated aggressively. Early identification of genital tract pathogens is important for the prevention and treatment of cervical cancer , 23, andIt is currently thought that genital tract infections are closely associated with age and sexual habits. An age-specific prevalence curve revealed that HPV infections first peak in women < 30 years of age, then decrease with age, but the curve surges again at approximately 50 years of age and peaks again in women ≥ 60 years of age , 37. AccIn recent years it has been shown that the time of sexual debut in the adolescent student population (15–24 years of age) in China is earlier and the proportion is increasing, and understanding the need for self-protection is inadequate . A questIn this study we found a greater incidence of genital tract pathogens in patients between 15 and 25 years of age in the Haikou gynecologic clinics, indicating an uptick in genital tract infections in this age range. It is more important to increase reproductive health knowledge from families, schools, and networks to give early reproductive health education to young women and encourage them adopt prudent reproductive health protective measures. Indeed, this is crucial to lowering reproductive tract infections and enhancing the reproductive health of women who are ready to have children. Small quantities of RNA and DNA, as well as tumor cells, may now be detected in peripheral blood using technological advances, such as circulating tumor cells (CTCs), circulating cell-free DNA (cfDNA), circulating HPV DNA, and miRNA. Circulating molecules and biomarkers have the potential to be a useful diagnostic and prognostic tool for cervical cancer . FurtherThe single hospital from which all of the patients were chosen was a limitation that may have reduced the ability to generalize the findings. Future studies should include subgroup studies on age and co-infections with HPV, CT, UU, and NG.Among Haikou gynecologic outpatients, UU is the genital tract infection with the highest detection rate. To prevent mixed infections from genital tract pathogens, integrated polymicrobial testing is warranted in HPV-positive carriers. Reproductive tract infections are on the rise in younger people, thus adolescent sexual health education must be improved.


Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents  and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention. Human papillomavirus (HPV) belongs to the family of Papillomaviridae, which are non-enveloped double-stranded circular DNA viruses with oncogenic potential .With regard to their oncogenic potential on infected epithelia, HPVs are classified into low-risk -(LR-) and high-risk (HR-) oncogenic genotypes ,2. LR-HPThe genome of HPV consists of six early genes  that encode proteins that are synthesized during initial infection and two late genes (L1 and L2) that encode proteins that are produced later on, after the synthesis of early proteins ,13. EarlNotably, young children may acquire HPV during childbirth from the mother’s genital tract, or during diaper care and when bathing, as a result of active outbreaks of warts on the caregiver’s hands or poor hand hygiene; however, an evaluation of all possible means of transmission, including sexual abuse, is required.A detailed multidisciplinary evaluation is required when managing AWs, including a complete physical and psychological examination, with particular attention to genital areas, always considering the possibility of sexual abuse ,4,7. AmoEspecially in young children, treatment is complicated by sensitive skin and frequent recurrences ,12,13,14Herein, we provide a review of the literature regarding currently available therapies for pediatric AWs and report an illustrative case of a two-year-old child with atopic dermatitis and AWs treated with topical podophyllotoxin.We performed a literature search of English reports on topical therapies available for the treatment of AWs in children on PubMed. To retrieve all relevant articles, the following terms were researched: “warts”, “anogenital warts”, “HPV”, “human papillomavirus”, “pediatric”, “children”, “childhood”, “treatment”, “therapy”, and “topical”.There was a special emphasis on the treatment of young (<12 years) children, keeping in view the fact that great difficulties exist in the treatment of this age group, as no topical treatment for AWs is licensed by the FDA for patients under age 12, and other, more aggressive therapies are poorly tolerated.Numerous therapeutic approaches are available for the treatment of AWs, with the primary aim of eliminating visible warts, yet with possible recurrences, as therapy does not clear the causative viral infection itself ,2. TreatPatient-applied topical therapies are reported to be well tolerated in children because of the low aggressiveness of single applications; however, these necessitate repeated sessions to achieve therapeutic results and can give rise to complications ,2. TheseIn detail, topical podophyllotoxin 0.5% is an antimitotic agent derived from purified podophyllin resin that inhibits the formation of microtubules. It is approved for the treatment of anogenital warts in adults , with a reported clearance rate of 45–88% and a recurrence rate of 12–60% ,19,21. TIn children, minimal irritation was reported with topical podophyllotoxin 0.5% application while still obtaining therapeutic efficacy. Moresi et al. reported 88% resolution of AWs in 17 children <2 years, without recurrence within 2–16 weeks of the use of podophyllotoxin 0.5% gel at the reduced dosage (tapered single week application) . FurtherImiquimod is an imidazoquinolin heterocyclic amine that induces the clearance of warts through local antiviral and antitumor properties, acting as a toll-like receptor-7 (TLR-7) agonist and stimulating local macrophages to produce cytokines, particularly interferon-α (IFN-α). Treatment is applied three times weekly once a day and is then left to act on the skin for 6–10 h, for up to 8–16 weeks ,21.Local inflammatory side effects are common, especially erythema, with itching, vesiculation, and ulceration, while flu-like symptoms occur less often ,21. In aSinecatechins are a green tea extract that was approved by the FDA in 2006 as a treatment for AWs with thrice daily application for up to 16 weeks in adult patients (>18 years) . In adulCidofovir is an antiviral agent used to prevent the replication of DNA viruses by blocking DNA polymerase. AW therapy with topical cidofovir 1–3% cream is rarely reported in children: one report described the clearance of resistant AWs, which had been non-responsive to cryotherapy, imiquimod, and podophyllotoxin, in a 6-year-old-girl treated cidofovir 3% cream . AdditioOther topical therapies include healthcare provider-administered cytotoxic agents such as trichloroacetic acid (TCA), podophyllin resin, and nitric-zinc complex (NZC). ,21.TCA 80–90% induces cell death by protein coagulation. It is applied weekly by health-care providers, directly onto warts, avoiding spreading the solution onto the surrounding skin, where it can cause ulceration. In adults, clearance rates of 70–81% were reported, with a recurrence rate of 36% . The usePodophyllin resin, administered by healthcare providers at 10–25%, is derived from the root of Podophyllum sp. and carries a risk of systemic side effects, including neurotoxicity, liver dysfunction, and bone marrow suppression. In adults, 38–79% response rate and 21–70% recurrence rates were reported. In children, the use of podophyllin resin is not recommended [Furthermore, 25% podophyllin in a benzoin tincture is available for the removal of soft genital AWs, though this is not FDA-approved. It is administered by healthcare providers. To avoid systemic absorption, dried 25% podophyllin should be kept in place for 1 to 4 h, then thoroughly removed.Provider-applied topical NZC also deserves to be mentioned. It is a recently developed topical solution containing 65% nitric acid, zinc, copper, and organic acids, exerting a caustic effect on AWs, with an 84–87% cure rate in wide population studies in adults ,33. CiccFinally, Interferon represents a healthcare provider-administered therapy; it can be used topically and intralesionally for treatment-resistant genital warts. However, it is not recommended as a first-line treatment because it is expensive, has uncertain effectiveness, and has not been tested on children .2) lasers are also used to treat resistant anogenital warts but are associated with pain and scarring and their availability is scarce. In adults, CO2-lasers yield 40–100% response rates and 4–77% recurrence rates [Among other healthcare provider-administered methods, physical destruction methods include cryotherapy, surgical removal, and laser vaporization . These ace rates . Therefoce rates ,36.Candida antigen, tuberculin/purified protein derivative (PPD), bacillus Calmette-Guerin (BCG) vaccine, and the measles, mumps, and rubella (MMR) vaccine, have been proven safe and effective for the treatment of cutaneous warts in children [Intralesional immunotherapies, including children .Additionally, for the treatment of AWs, these intralesional immunotherapies are promising and cause only mild and transient adverse effects, including localized inflammation at the injection site and flu-like symptoms due to the induced  release Candida antigen injection and 73% after MMR injection [Recently, Nofal et al. reported complete regression of multiple AWs in 80% of children after njection .Currently, HPV vaccination is not recommended as a treatment for established HPV infection and HPV-related disease, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and would plausibly, if confirmed, represent the beginning of a new era for the management of HPV-induced AWs . Indeed,Indeed, a relevant effect on AWs of worldwide-adopted HPV vaccination programs has been observed already . Recent HPV vaccines were originally developed as a primary prevention measure to reduce HPV infection rates and HPV-related tumors and were rapidly established as a successful prevention measure of anogenital cancer and AWs. In 2006, the FDA approved a quadrivalent HPV vaccine (Gardasil) that targets HPV genotypes 6, 11, 16, and 18. A bivalent HPV vaccine (Cervarix) targeting only HR-HPV genotypes 16 and 18 was approved in 2009 . In 2014It must be specified that, so far, controversial results about a possible therapeutic role of HPV vaccination have been reported. Kreuter reported no therapeutic efficacy of quadrivalent HPV vaccination in adults and pediatric patients with AWs ,46.Conversely, numerous literature data suggest a possible therapeutic effect of HPV vaccination on existing HPV infection and HPV-induced benign proliferations, including AWs and cutaneous warts (CW) ,50,51,52The exact mechanism influencing the therapeutic effect of HPV vaccines has not yet been explored. The efficacy of commercially available HPV vaccines is based on their ability to induce a humoral immune response ,59. HoweSystematic studies analyzing the possible therapeutic effects of HPV vaccination on AWs and other HPV-induced epithelial proliferations are required to gain a deeper understanding of the still puzzling immune mechanisms underlying the possible clearance of HPV-related lesions after HPV vaccination and to establish a potential therapeutic role of the vaccine in recalcitrant HPV-proliferations . Indeed,A two-year-old boy presented at the Dermatology Unit with proliferative, warty, slightly pruritic, perianal tumors which had been worsening for one year. The child, delivered vaginally at term, had a history of atopic dermatitis, hyper-eosinophilia, and food allergy to eggs, fish, and bananas.Clinical examination evidenced multiple perianal, hyperkeratotic, skin-colored papules 1–3 mm in diameter, partially coalescing into plaques; no mucosal alterations were evidenced . DiagnosThe child was administered topical podophyllotoxin 0.5% once a week for 30 days by the caregiver at home, obtaining complete clinical remission of AWs after one month of therapy, without irritation or other adverse effects. Additionally, at clinical follow-up after 3 and 6 months, no recurrences were evidenced.Written informed consent to the publication of case details was obtained.HPV is an epitheliotropic virus, specifically infecting cutaneous surfaces and mucosae, including the vulva, vagina, cervix, penis, anus, and oropharynx ,68,69,70Accordingly, AWs represent benign epithelial proliferations associated mainly (90%) with LR-HPV infection genotypes 6 or 11, while in up to 10% of cases, HR-HPV coexists, possibly leading to the development of malignant squamous cell carcinoma in a minority of cases . MoreoveRegarding the prevalence and persistence of the causative HPV infection, data are disparate and highly influenced by anatomic site, age, sex, HPV genotype, and other risk factors for viral persistence, including number of sexual partners and smoking . In a reRemarkably, anogenital HPV infection is mainly transmitted sexually in adults, occurring in more than 40% of sexually active women and representing the most common STI ,67,71. CAlthough the identification of pediatric anogenital warts should always alert physicians to the possibility of sexual abuse, it must not be considered pathognomonic. Indeed, in young children (<4 years) with no other STI and no evidence of anogenital trauma or clinical indicators of physical abuse, HPV is most likely non-sexually acquired . Girls aHPV transmission in young children is hypothesized to occur either “vertically” or, more predominantly, “horizontally” ,76. VertOf note, children can become affected during diaper care and when bathing as a result of active outbreaks of warts on the caregiver’s hands’ or poor hand hygiene. Furthermore, indirect horizontal transmission through towels, linings, and personal hygiene products has been theorized, though this route is considered to have little impact .Notably, in atopic dermatitis, impaired local immune response and altered skin barrier may favor viral infection and persistence ,17. AddiRecently, the previously mentioned potential therapeutic effect of HPV vaccination on AWs has raised interest in this research field due to the compelling prospect of possibly obtaining both primary HPV prevention as well as targeted HPV treatment ,64,65,66Especially in children, a potential dual role of HPV vaccination, i.e., therapeutic and preventive, seems plausible and compels us to obtain in-depth insight into possibly unexplored potentialities of the HPV vaccine. Yet, to date, the authors note that HPV vaccination is not recommended as a treatment for established HPV infection and HPV-related diseases such as AWs . The maiIn the meantime, HPV-therapeutic vaccines are also under trial for use in cervical cancer and cervical intraepithelial neoplasia (CIN), AIN, and VIN, but at present, no HPV-specific antiviral treatment is available, nor can therapies adopted to remove AWs reliably eradicate HPV infection ,50. IndeConsequently, to date, considering the high number of recurrences due to latent viral infection, only limited cases of AWs warrant a therapeutic approach, as in the described illustrative case, which presented symptomatic AWs that worsened for one year. In our experience, as highlighted by the presented case in point, at-home topical therapy is preferred as an alternative to more aggressive healthcare provider-administered therapies. Indeed, it must be considered that especially young children have difficulties in tolerating the pain related to healthcare provider-administered therapies ,2,3. FurConclusively, a patient-tailored approach is necessary when dealing with AWs, especially in young children, whose history might be complex and for whom a cure might be impaired by sensitive skin and frequent recurrences ,2,3,81. Additionally, it is important to consider that children have low pain tolerance, possibly influencing their compliance to some therapies, mainly aggressive ones. Therefore, pediatric AWs should be treated with low aggressiveness therapies, such as mild repeated domiciliary topical therapies that can be effective and safe in pediatric Aws, even if atopic dermatitis and related skin barrier defects coexist, representing a valid alternative to painful, aggressive treatments.Lastly, though HPV vaccination is not recommended as a treatment for AWs, a possible therapeutic role of HPV vaccination has been reported which highlights the need to obtain a more in-depth understanding of the possibly unexplored therapeutic potentialities of the HPV vaccine.


HPV vaccine coverage in France remained lower than in most other high-income countries. Within the diagnostic phase of the national PrevHPV program, we carried out a mixed methods study among school staff to assess their knowledge, beliefs and attitudes regarding HPV, HPV vaccine and vaccination in general, and regarding schools’ role in promoting HPV vaccination.n = 301), analysed using descriptive statistics; and (ii) qualitative data from three focus groups (n = 14), thematically analysed.Middle school nurses, teachers and support staff from four French regions participated between January 2020 and May 2021. We combined: (i) quantitative data from self-administered online questionnaires  who participated in the focus groups were unfavourable to offering vaccination at school because of parents’ negative reactions, lack of resources, and perceived uselessness.These results highlight the need to improve school staff knowledge on HPV. Parents should be involved in intervention promoting HPV vaccination to prevent their potential negative reactions, as feared by school staff. Several barriers should also be addressed before organizing school vaccination programs in France.The online version contains supplementary material available at 10.1186/s12889-023-15342-2. Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, and a major public health issue , 2. VaccAs part of the PrevHPV program, strengthening the role of schools in promoting HPV vaccination has been identified as a promising way to improve VC , 9. SchoStrengthening the role of school in promoting HPV vaccination require buy-in from all school stakeholders, including teachers, school health staff , administrative and support staff . TogetheIn this context, as part of the diagnostic phase of the PrevHPV program, we carried out a mixed methods study among school staff to assess their knowledge, beliefs and attitudes regarding HPV, HPV vaccine and vaccination in general, and regarding the role of school in promoting HPV vaccination. The aim was to identify barriers and facilitators, as well as needs of the different school professionals who could be involved in the development and the implementation of interventions promoting HPV vaccination in French middle schools.We conducted a concurrent mixed methods study  combininThis study was conducted among school staff  from middle schools . We selected schools located in four regions (out of 13 regions in mainland France), hereafter called “study regions”, where the PrevHPV teams were settled and representing a diversity of geographical, demographic and socioeconomic contexts as well as HPV vaccine coverage rates : Ile-de-This study was part of study *C19-54* conducted under the responsibility of Inserm. It was granted approval by Evaluation Committee of Inserm, the Institutional Review Board  on 10 December 2019. All study participants gave their informed non opposition to participation, in line with French legal guidelines. This study follows the COREQ  and the STROBE  reporting guidelines /others. Then, we contacted the head of each middle school by email/phone to ask him/her to participate in the study. As we aimed to recruit 30 to 40 middle schools, we first selected 80 schools (expected acceptation rate: 50%) and planned to select additional schools if needed.Heads of the schools who accepted to participate informed all school staff of the study and sent them the link to the online questionnaire (expected duration: 15 min). Participation of the school staff in the online quantitative survey was voluntary and not compensated.School staff interested in participating in a focus group were invited to contact the research team by email. The participant information sheet attached to the invitation stated that participants to the focus groups would be offered a 20€ shopping voucher.yes, no, unsure) and one item on whether cervical cancer is due to a persistent HPV infection ;- knowledge about HPV infections: 10 items ;- knowledge about HPV prevention and vaccination: 12 items (strongly disagree to 7 = strongly agree);- psychological antecedents of vaccination, assessed using the long-version of the 5C  scale : 15 itemyes, no, unsure) and, if no or unsure, acceptability to receive HPV vaccine if it was possible and recommended for them ; appropriate period to propose HPV vaccination among pupils .- personal vaccination status and attitudes towards HPV vaccination: being vaccinated against HPV  they discuss with pupils each of nine different public health topics, including vaccination.We also collected data on demographic personal and professional characteristics  and practices, i.e. the frequency . Each focus group was conducted by two members of the study group  trained in qualitative research interviews. After an oral consent, all the focus groups were recorded and transcribed.p value of  < 0.05 for two-sided tests was considered significant. All analyses were performed with SAS V.9.4 .Descriptive statistics were used to describe characteristics of the participants and their responses to the online questionnaire. Quantitative variables are presented as means and standard deviations and categorical variables as numbers and percentages. Knowledge, beliefs and attitudes are presented overall and by profession which are compared by using Chi2 or exact Fisher tests and ANOVA for respectively categorical and quantitative variables. A A thematic analysis was used to analyse transcripts of the focus groups. An analysis grid was developed by members of the study group . Each theme and subtheme were discussed until a consensus was reached. Each focus group was then coded according to this grid.Finally, this mixed approach used a merging data approach  to combiThree hundred and one participants from 17 different schools completed the online questionnaire . About half of them were teachers and one third school nurses. Most 84%) respondents were women and 49% were older than 45 years  were conducted (duration: 50 min to 2 h). Most participants (11/14) were women; 5 were school nurses, 4 teachers and 5 support staff (Table Most (80%) respondents to the questionnaire knew that HPV is a sexually transmitted infection that concerns both female and male Table . Less thParticipants to the focus groups felt very poorly informed about HPV Table , that thAlmost 90% of the respondents to the questionnaire knew the existence of the HPV vaccine and 56% knew that it is recommended for heterosexual boys in France Table . RegardiParticipants to the focus groups were also aware that a vaccine against HPV exists but had some misunderstandings about its schedule, especially the reason why it is recommended before the first sexual relationships and for boys Table . Some paRespondents to the questionnaire showed high confidence in vaccination and had positive attitudes towards collective benefits of vaccination . Barriers to vaccination for themselves (complacency and perceived constraints) were low with mean scores < 2.5 . They get new information through personal research or the media Table .The questionnaire results showed that vaccination was the public health topic least frequently discussed at school, including by nurses  have a high level of confidence in vaccination in general. However, we also found that past controversies around vaccination fueled doubts about vaccines safety and impaired trust towards French authorities. Restoring trust in vaccination remains challenging and “one size fit all intervention” does not exist , but FreThis mixed methods study highlighted the need to improve school staff knowledge on HPV and its vaccination, and the perceptions of teachers and support staff about the role of schools in educating pupils on this topic in France. It also provides key findings on the barriers that should be addressed before organizing HPV school vaccination programs in France.Additional file 1: Additional Table 1. Teams conducting the PrevHPV program (The PrevHPV Consortium). Additional Table 2. COREQ  Checklist. Additional Table 3. STROBE  Statement — checklist of items that should be included in reports of observational studies. Additional Table 4. Characteristics of the middle schools invited to participate in the study and of those which accepted to participate. Additional Table 5. Additional illustrative verbatim of participants to the focus groups. Additional Table 6. Psychological antecedents of vaccination  among participants to the self-administered online questionnaire and by profession. Additional Table 7. Public health topics discussed with pupils by participants to the self-administered online questionnaire and by profession. Additional Table 8. Appropriate period to propose HPV vaccination among pupils according to participants to the self-administered online questionnaire and by profession. Additional Document 1. Self-administered online questionnaire. Additional Document 2. Focus groups’ interview guide. Additional Document 3. Names of the PrevHPV Study Group’s members.


Recently, it has been suggested that microbial infections play a role in the pathogenesis of endometriosis. One of the most commonly suggested infections associated with the pathogenesis of endometriosis is human papillomavirus (HPV) infection. The present study is aimed at evaluating the prevalence, types, and risk factors for HPV infection in women with endometriosis and at investigating the association of upper and lower genital tract involvement with HPV and the severity of endometriosis. t-test for continuous variables.  This cross-sectional study was conducted on 81 patients with endometriosis, referred to Rasool Akram Medical Complex in Tehran, Iran, for laparoscopic surgery. The patients' demographic, clinical, and anthropometric data were extracted from their medical records, as well as interviews. The stage of disease was scored based on the revised American Society for Reproductive Medicine (rASRM) classification. The HPV-positive and HPV-negative cases were compared using the chi-square test for categorical variables and Student P = 0.014). The VAS scores for dysmenorrhea and dyspareunia were relatively the same in the two groups (P > 0.05). HPV 6 and HPV 11 were the most common types of HPV, reported in 35% and 30% of endometriosis cases, respectively.  Twenty (24.69%) out of 81 women with endometriosis were infected with HPV . The HPV-infected women had a significantly lower infertility rate (15% vs. 45.9%;  The prevalence of HPV was 24.69%, and low-risk genotypes were dominant. No significant association was found between HPV and the severity of endometriosis. Endometriosis, which refers to the presence of endometrium outside the uterine cavity, can occur in the pelvis or outside the pelvic cavity . It is cStreptococcus, and Escherichia coli bacteria across various microbiome sites .Demographic, clinical, and anthropometric data of the patients, including age, body mass index (BMI), gravidity, parity, diagnosis time, uterus size, dyspareunia, dysmenorrhea, chronic pelvic pain, history of surgery, infertility, and menstrual status, were extracted from the patients' medical records, as well as interviews. Moreover, the stage of disease was scored by surgeons, based on the revised American Society for Reproductive Medicine (r-ASRM) classification. Deep endometriosis (DE) was considered a special form of endometriosis, infiltrating more than 5 mm below the surface of the peritoneum. Ovarian endometrioma (OMA) and the presence of nodules in the rectum, uterosacral ligament, and bladder were also recorded. Before the onset of laparoscopic surgery, a sample of the exocervix was collected from the cervical mucus to examine the presence of HPV, using a sterile Ayre spatula and a cytobrush .After the onset of surgery and determining the severity of endometriosis, to detect HPV in the cul-de-sac, a tissue biopsy was obtained from the uterosacral ligament by a surgeon and immediately placed in saline solution; after it was stored in a refrigerator at -20°C, it was sent to a laboratory. This tissue biopsy used for identifying HPV in the cul-de-sac was called pelvic HPV. The HPV Direct Flow CHIP was used for screening HPV types and genotyping HPV types by polymerase chain reaction (PCR) assay, followed by reverse dot-blot automatic hybridization based on the DNA Flow Technology .t-test for continuous variables. Data were analyzed in Stata 14 . The significance level was considered to be less than 0.05.To describe the demographic and clinical characteristics of HPV-positive and HPV-negative patients, mean and standard deviation were measured for continuous variables and frequency and percentage for categorical variables. Fisher's exact test was performed for data analysis. The two groups were compared using the chi-square test for categorical variables and Student In this study, a total of 81 women with endometriosis were included. Twenty women (24.69%) were infected with HPV, nine women with pelvic HPV, nine women with vaginal HPV, and nine women with both pelvic and vaginal HPV .P > 0.05). Although HPV-infected patients had higher rates of irregular menstrual cycles (45% vs. 40.98%) and rectal nodules (95% vs. 86.89%) and non-HPV patients had a higher rate of uterosacral involvement (82.25% vs. 70%), the differences were not statistically significant (P > 0.05). However, HPV-infected women had a significantly lower rate of infertility compared to noninfected women .In Overall, 31 patients (38.27%) were infertile (17.28% with primary infertility and 20.99% with secondary infertility).P = 0.003). The VAS scores for dysmenorrhea and dyspareunia were relatively the same in the two groups (P > 0.05)  .P = 0.93). . .In P > 0.05).In HPV 6 and HPV 11, reported in seven and six patients, respectively, were the most common types of HPV in endometriosis patients. In In the current study, the presence and genotypes of HPV were first investigated in confirmed cases of endometriosis, using HPV Direct Flow CHIP and PCR assay. Secondly, HPV-positive and HPV-negative groups were compared in terms of the baseline and clinical variables. The findings indicated that low-risk HPV was more prevalent in the study population. However, HPV was not associated with the severity of endometriosis, age, BMI, parity, disease duration since diagnosis, uterus size, history of surgery, urinary signs, menstrual status, or treatment method. Rectal nodule, uterosacral nodule, bladder nodule, and dysmenorrhea and dyspareunia indicate severity of endometriosis. Also, dysmenorrhea and dyspareunia were not significantly different between HPV-positive and HPV-negative groups, suggesting that HPV does not affect the severity of symptoms in endometriosis. According to studies conducted in Japan, China, and Turkey, there is a significant difference regarding the microbiota between women with and without endometriosis .The prevalence of HPV infection in patients with endometriosis has been evaluated in the literature; nevertheless, the results vary between studies –21. In tAdditionally, in a study in Iran, Heidarpour et al.  investigThe most common types of HPV in women with endometriosis were type 6 and type 11, which are both categorized as low risk. However, findings from other countries suggest different distributions for virus genotypes in endometriosis patients. In a study by Rocha et al. , HPV 16 Considering the pathophysiology of endometriosis, the possible role of infectious agents, such as HPV, in the development of endometriosis needs to be further examined. Genetic and epigenetic alterations, as well as the effects of infection on immunity and angiogenesis, can be caused by bacteria, viruses, and other microorganisms and lead to endometriosis lesions , 27. CurIn another study, Oppelt et al. reported that there is no definite information on whether HPV infection is associated with an increased incidence or risk of endometriosis. They showed that HPV might not be involved in the etiology of endometriosis, although it could promote transformation into a carcinoma . OverallThe main limitation of this study was its cross-sectional design. Data on specific changes due to HPV would be more reliable if there was a control group for comparison. Also, considering the sexually transmitted nature of HPV, data on the sexual habits of the participants and the number of their partners were required, which can be challenging to collect. On the other hand, the strength of this study was the homogeneity of the participants' genetic and ethnic characteristics.The prevalence of HPV was estimated at 24.69% in this study, and low-risk genotypes were dominant. The baseline characteristics of women did not differ significantly between infected and noninfected groups. Also, dysmenorrhea and dyspareunia were not significantly different between the groups, suggesting that HPV does not affect the severity of pain or disease in endometriosis patients. The association between HPV and endometriosis was not directly calculated, and it is recommended to conduct further cohort studies to conclusively confirm if endometriosis lesions are related to HPV infection.


Vaccination against human papillomavirus (HPV) is critical to the prevention of HPV-associated cancers. This study aimed to describe the reasons patients cited for not initiating or completing the HPV vaccination series, as reported by health-care professionals.Study data were obtained from a University of Texas MD Anderson Cancer Center population-based cross-sectional survey of health-care professionals practicing in Texas. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated by patient population (parents of children and adult patients).The study included 973 primary care clinicians, of whom 45.53% were physicians and 54.47% were midlevel care professionals. For parents who did not initiate HPV vaccination for their child, the most commonly cited reasons were the belief that the vaccine was not needed , that the child was not sexually active , and safety concerns/side effects . Among age-eligible adults who did not initiate HPV vaccination, lack of knowledge and awareness was the most commonly cited reason . For noncompletion of the HPV vaccine series, parents most commonly cited competing priorities , followed by adverse reactions after the first dose . Similarly, for noncompletion of the HPV vaccine series among adults, competing priorities was the most cited reason .These findings highlight the importance of addressing misconceptions and improving education about HPV vaccination to increase vaccination uptake rates and prevent HPV-related cancers. Human papillomavirus (HPV) is a sexually transmitted infection associated with several cancers, including cervical, anal, penile, and oropharyngeal cancers . HPV vacSeveral studies have investigated the reasons parents and patients cite for not initiating or completing HPV vaccination . CommonlThe state of Texas has one of the lowest HPV vaccination rates in the United States , which mThe study data were obtained from a population-based cross-sectional survey developed at the University of Texas MD Anderson Cancer Center and conducted between January and April 2021. The target population for the survey included all health-care professionals currently practicing in Texas. Health-care professionals were defined as physicians with an MD or equivalent degree in the specialties of internal medicine, family medicine, obstetrics/gynecology, and pediatrics as well as physician assistants and nurse practitioners. A list of all health-care professionals currently practicing in Texas at the time of the study was obtained from the LexisNexis master referential database under an annual license. The database also contains the email address and a few demographic characteristics of these professionals, including their sex and practice type . All eligible health-care professionals were sent an email invitation to complete an online health-care professional survey. All health-care professionals provided informed consent. A total of 1283 health-care professionals completed the study, accounting for a response rate of 7%. There was no statistically significant difference between respondents and nonrespondents regarding health-care professional sex and practice type, the 2 variables for which data were available for nonrespondents in the LexisNexis database. The study was approved by the MD Anderson Cancer Center Ethical Review Board (IRB No. 2019-1257) and followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines to ensure the ethical and scientific integrity of the research.Health-care professionals were identified based on the patient population they serve, which allowed us to assess study measures for 2 distinct patient populations: 1) parents of children eligible for HPV vaccination and 2) adult (aged ≥18 years) patients. Health-care professionals who indicated that they serve “only children” or “children and adults” were then asked to select all that applied from a set of possible reasons parents cited for 1) not initiating HPV vaccination, using the survey question “Which reasons do PARENTS cite for NOT initiating HPV vaccination in their child?” and 2) not completing the HPV vaccination series, using the survey question “Which reasons are cited by PARENTS for NOT completing recommended HPV vaccination series for their children?” See the survey questionnaire in the Our analysis was restricted to health-care professionals practicing in facilities that offer HPV vaccination to age-eligible patients (children and adults older than 18 years of age). The baseline characteristics of health-care professionals in our study were estimated using survey frequencies. Estimates were stratified by patient population (parents of children and adult patients) and by HPV vaccination initiation and completion. Furthermore, estimates were stratified by health-care professional characteristics. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated with corresponding 95% confidence intervals (CIs). All analyses were conducted using Stata/IC, version 15.1, statistical software .The study comprised 973 primary care clinicians, of whom 443 (45.53%) were physicians and 530 (54.47) were mid-level care professionals, with 103 (10.79%) younger than 35 years of age, 589 (61.68%) 35 to 54 years of age, and 263 (27.54%) 55 years of age or older. Of the total number of health-care professionals, 282 (28.98%) worked in university/teaching hospitals, 325 (33.40%) were in group practices, and 120 (12.33%) were in in federally qualified health centers or public facilities .Results revealed that the most commonly cited reasons were the beliefs that their child was not sexually active  and that the vaccine was not needed . Safety concerns and side effects were also commonly cited, at 47.05% (95% CI = 43.44% to 50.69%), whereas lack of knowledge and awareness about the HPV vaccine was cited by 44.31% (95% CI = 40.73% to 47.94%) of parents .Among age-eligible adults who did not initiate HPV vaccination, lack of knowledge and awareness was the most commonly cited reason, at 30.52% (95% CI = 27.71% to 33.50%), followed by the belief that the vaccine was not needed, at 24.77% (95% CI = 22.15% to 27.58%) .For parents who did not complete the HPV vaccine series for their child, competing priorities was the most commonly cited reason, at 41.29% (95% CI = 37.76% to 44.91%), followed by adverse reactions after the first dose, at 16.05% (95% CI = 13.56% to 18.90%) .Among age-eligible adults who did not complete the HPV vaccine series, competing priorities were the most common reason cited, at 31.04% (95% CI = 28.20% to 34.02%), followed by out-of-pocket cost, at 14.59% (95% CI = 12.51% to 16.96%) .Finally, reasons that adults and parents cited for not initiating and completing the vaccination series in their child stratified by health-care professional sex, age, and practice type are provided in Study results revealed that cited reasons varied by HPV vaccination initiation and completion as well as by whether the respondent was a parent or age-eligible adult patient. The results of this study indicate that lack of knowledge and awareness about the HPV vaccine and the perception that the vaccine is not needed were the most common reasons cited for not initiating the vaccination series among age-eligible adults. These findings are consistent with previous studies, which have identified low knowledge and awareness of the HPV vaccine as a major barrier to vaccine uptake ,5. More Study findings also revealed that sexual activity status and concerns about safety and side effects were most commonly cited by parents as reasons for not initiating the HPV vaccination series. At the national level, safety concerns/side effects is consistently the leading reason for HPV nonvaccination; however, as shown by our study findings, misperceptions about the interaction between sexual activity and HPV vaccination persist in Texas . The citCompeting priorities were the most commonly cited reason for not completing the HPV vaccination series among parents and age-eligible adults. This finding may stem from the HPV vaccine series requiring multiple doses, which can be difficult for families to complete because of scheduling conflicts or other barriers. Single-dose HPV vaccination, which has been shown to be efficacious , could eThis study is not without limitations. First, health-care professional biases, such as their philosophical ideologies  could influence their response to the survey. Similarly, consistent with most surveys of health-care professionals , the resOverall, the findings of this study underscore the importance of addressing the barriers to HPV vaccine uptake, particularly low knowledge and awareness about the vaccine and safety concerns. Through targeted education and outreach efforts, health-care professionals can be adequately equipped to address misconceptions and concerns about the HPV vaccine and promote the importance of HPV vaccination both for children and for adults. Addressing safety concerns through education and encouraging open communication with health-care professionals may alleviate vaccine hesitancy.pkad047_Supplementary_DataClick here for additional data file.


HPV, or Human Papilloma Virus, has been the primary causative agent of genital warts and cervical cancer worldwide. It is a sexually transmitted infection mainly affecting women of reproductive age group, also infecting men and high-risk group individuals globally, resulting in high mortality. In recent years, HPV has also been found to be the major culprit behind anogenital cancers in both gender and oropharyngeal and colorectal cancers. Few studies have reported the incidence of HPV in breast cancers as well. For a few decades, the burden of HPV-associated malignancies has been increasing at an alarming rate due to a lack of adequate awareness, famine vaccine coverage and hesitancy. The effectiveness of currently available vaccines has been limited to prophylactic efficacy and does not prevent malignancies associated with post-exposure persistent infection. This review focuses on the current burden of HPV-associated malignancies, their causes and strategies to combat the growing prevalence of the cancers. With the advent of new technologies associated with treatment pertaining to therapeutic interventions and employing effective vaccine coverage, the burden of this disease may be reduced in the population. Human Papilloma Virus (HPV) is one of the most common causes of sexually transmitted infections worldwide. It is the main etiological agent responsible for multiple types of cancers, primarily cervical cancer in women. HPV is a small, non-enveloped, double-stranded DNA virus infecting the skin and mucosal surfaces. It is classified into two categories: low-risk HPVs (Lr-HPVs) and high-risk HPVs (Hr-HPVs). Lr-HPV is responsible for the manifestation of anogenital and cutaneous warts, while Hr-HPV is majorly responsible for oropharyngeal  cancers and anogenital cancers, including cervical, anal, vulvar, vaginal and penile cancers ,2,3,4,5.Globally, Cervical cancer is the primary cause of cancer-related mortality among women of reproductive age. Vaccination against HPV is the safest and the most reliable means of primary prevention of cervical carcinoma. Currently, there are three major vaccines available worldwide for HPV; Cervarix, Gardasil and Gardasil 9. But due to the high cost, these vaccines are not accessible to women in developing countries. The age-standardized incidence ratio for cervical cancer in the world is 14 per 100,000 women, while in India, it is 22, which is significantly higher in comparison ,7. More It is crucial to have a clear epidemiological knowledge of the distribution of cervical human papillomavirus infection in the general population. This knowledge is important to devise vaccine strategies and assess the case burden of HPV over a period of time. Genital HPV infection is one of the most common sexually transmitted infections worldwide. On the basis of cross-sectional observations and meta-analysis done in 2007, it was found that approximately 10% of women worldwide with normal cytological findings through traditional methods carry a detectable cervical HPV infection, although a broad range of estimates (6.1–35.5%) has been documented, depending on the HPV testing technology, study size, the age groups and geographical region studied ,19.A second meta-analysis done in 2010 among 100 thousand women from 59 countries found the prevalence of HPV infection among women with normal cytological findings to be 11.7% (adjusted) .HPV-associated malignancies commonly manifest in the form of cervical, vulvar, anal, colorectal and oropharyngeal cancer. Nearly all cases of cervical cancer can be attributed to HPV infection. Although most HPV infections clear up on their own and most pre-cancerous lesions resolve spontaneously, there is a risk for all women that HPV infection may become chronic and pre-cancerous lesions progress to invasive cervical cancer. HPV being the oncogenic virus, modulates most of the hallmarks of cancer  22]. HP. HP22]. Cervical cancer is the main cause of cancer-related mortality among women worldwide. A study conducted by Munoz et al. pooled data from 11 case-control studies to determine the association between cervical cancer and HPV infection from multiple countries; 15 HPV types have been classified as high risk, three have been classified as probable high-risk, 12 have been classified as low risk and three are considered to have an undetermined risk based on the progression to cervical cancer . The curPersistent infection of HPV leads to the progression of cervical carcinoma . HPV cauLactobacillus sp. , while CST-IV comprised higher level of anaerobic bacteria like Gardnerella, Atopobium, Prevotella, Mobiluncus, Streptococcus, Mycoplasma, Sneathia and Ureaplasma [Lactobacillus species and higher levels of anaerobic species, causing a disturbance in vaginal homeostasis resulting in Bacterial vaginosis (BV). The increase in cervicovaginal pH and reduction in lactic acid-producing bacteria disturbs the normal microflora and induces the growth of atypical bacterial growth. BV is known to be associated with an increased risk of HPV infection and subsequent progression to cervical intraepithelial neoplasia. BV is associated with an increase in proinflammatory cytokines and a decrease in levels of SLPI (Secretory leukocyte protease inhibitor), an anti-inflammatory cytokine that causes changes in the immune system, increasing the chances of infection with HPV. Additionally, oxidative DNA damage associated with BV results in the generation of ROS, which cause DNA breaks in the host genome and HPV episome, enhancing viral acquisition and integration and resulting in neoplastic transformation similar to that employed by the HPV E6 oncoprotein [Lactobacillus sp. resulting in lower chances of HPV acquisition and enhanced HPV clearance. On the contrary, an increase in anaerobic species like Gardnerella results in a higher rate of HPV acquisition, the persistence of HPV infection and progression to cervical carcinogenesis [L. iners is one of the species of lactic acid-producing bacteria known to enhance dysbiosis and is correlated with a high frequency of HPV infection [The mucosal surface of the female reproductive system is the primary site of HPV infection. The mucosal system acts as the first line of host defense in eliminating the risks of any probable infections, including HPV . Vaginaleaplasma . Vaginaloprotein . Multiplogenesis ,62,63,64nfection .Apart from this, epigenetic factors like microRNAs (miRNAs) also modulate the gene expression and function in HPV-induced cervical cancer. miRNAs, a group of small non-coding RNA, are involved in the pathogenesis of cervical cancer by posttranscriptional regulation of gene expression. miRNAs in cervical cancer may act as OncomiRs or Tumor suppressor miRNAs. OncomiRs or oncogenic miRNAs regulate the function of tumor suppressor genes by inhibiting them, thereby inducing carcinogenesis, while dysregulation of Tumor Suppressor miRNAs results in the upregulation of oncogenes resulting in malignant transformations . As a reHead and neck cancer is the sixth most commonly diagnosed cancer. It is majorly attributed to smoking habits and the use of tobacco. However, recent studies have demonstrated HPV as one of the main causes of oropharyngeal cancer, the prime suspect being the HPV-16 genotype . HPV-DNAAmong all cancers, oropharyngeal squamous cell carcinoma or OPSCC has one of the most rapidly rising incidences in high-income countries ,78. In 2Hr-HPV is always considered to be the major contributor to cervical cancer, likewise, with growing evidence for oropharyngeal and colorectal cancer. However, the relationship of HPV with vulvar and vaginal cancers is still debatable and lacks contemporary information about the prevalence of HPV-associated malignant transformations, its precursor lesions and the identification of HPV status in the prognosis of malignancy.Vulvar squamous cell carcinoma, or VSCC, is typically a rarer form of malignancy, accounting for 4–6% of all gynecological cancers . There aVaginal cancer is a rare form of malignancy, mostly resulting the metastatic invasions from other sites . OverallAnal cancer is a rare form of malignancy, accounting for less than 5% of all gastrointestinal cancers . They arp < 0.0001) [Colorectal cancer (CRC) is one of the common malignancies occurring predominantly in the male population in the world. Multiple risk factors owing to the progression of malignancy in CRC, like genetic predisposition, have been documented, but the molecular mechanisms associated with the same have not been fully explored yet. The association between HPV infections and CRC has been controversial and inconclusive, owing to the different outcomes obtained in multiple studies. Previous reports have shown a positive association between HPV infection and the increased risk of CRC ,112,113. 0.0001) . This daApart from the major cancers discussed above, HPV is known to be linked to breast cancer, penile cancer, ovarian cancer, renal adenocarcinomas, lung cancer, liver and even brain, although the studies associated with them are relatively fewer, and the mechanism behind HPV mediated malignant transformations in these malignancies remain elusive.Breast cancer is the most common cancer type among women worldwide, attributing to the highest cancer-related mortality. According to estimations, more than 2 million new cases of breast cancer and 684,996 deaths were recorded to this malignancy . RecentlPenile Cancer is a rare form of malignancy contributing to 0.1–1 in 100,000 men in high-income countries . It makeOvarian cancer, though rare, is a life-threatening malignancy occurring in women. The association between ovarian cancer and HPV infection is ambiguous. It is widely known that HPV is the main causative agent behind cervical cancer; however, its role in carcinogenesis in ovaries is under studied and conflicting. A meta-analysis published in 2021 investigated 29 studies consisting of 2280 cases of ovarian cancer and reported a 15.9%  pooled prevalence of HPV. The low prevalence might be due to the affinity of HPV to infect certain squamous cells of the cervix . The preHPV detection in renal cell carcinomas and metastasis to the lungs, liver and brain is contradictory in various studies; however, it may be possible due to the association between major malignancies like oropharyngeal, head and neck cancer and cervical cancer metastasis with HPV ,157,158.HPV-associated research has led to the preparation of vaccines against the HPV virus, thereby paving the way for a decrease in the burden of HPV infections and associated cancers, majorly cervical carcinoma. Currently, there are three HPV vaccines targeting two, four or nine HPV types, which account for 70–90% of HPV-related cancers. All three of these vaccines are efficacious at preventing HPV infection in randomized trials and represent one of the first primary cancer prevention approaches on a global scale. Currently, at least 118 million women have received one dose of the HPV vaccine. This number is encouraging but only represents 3.5% of the world population ,160. TheHPV oncoproteins E6 and E7 are responsible for affecting the DNA damage checkpoint controls on interaction with p53 and pRb proteins resulting in unregulated growth and malignancy in the cells. The replication of HPV occurs in differentiated cells by maintaining a low copy number in basal epithelial cells. Due to this low copy number, HPV undergoes immune evasion from the host immune system and may elicit a typically weak immune response . Persist® 9 could prevent 90% of HPV-related cervical cancer cases and 50% of all other HPV-related malignancies [There are two types of vaccines that work against viral infections; Prophylactic vaccines and Therapeutic vaccines ,170. Prognancies . The maignancies . CurrentE6 and E7 oncoproteins are the preferred targets for developing therapeutic vaccines owing to their role in the onset and maintenance of malignancies and higher expression in HPV infection and precancerous lesions, which is limited to the infected cells and lesions . AdditioE1 and E2 are ideal targets for early viral infections as they are expressed before viral integration in the genome. Targeting these oncoproteins will be a preferable strategy to develop therapeutic HPV vaccines as the approach will generate cytotoxic (CTL) responses and strong tumor-specific T-cell responses to eliminate infected and malignant cells ,179,180.The combination of prophylactic vaccines and therapeutic vaccines also presents an effective strategy for vaccination among young women and older women who have been previously exposed to HPV infection. The combination therapy will be beneficial in generating short-term and long-term immune responses among this population. Chimeric proteins and pseudovirions are used as delivery vehicles for DNA vaccines employed in combination vaccination .With the increasing burden of malignancies associated with HPV, it is necessary to develop therapeutic vaccines that will help in eliminating long-term infection and targeted approaches to the prevention of cancer. Numerous clinical trials have shown promising results in the development of therapeutic vaccines, thereby paving the way for multiple approaches to the elimination of the HPV-related cancer burden.Vaccines have proved to be an important milestone in the prevention of HPV-associated malignancies, predominantly cervical cancer. However, due to the increasing burden of these malignancies and the surging demand for therapeutic vaccines to overcome the limitations associated with prophylactic vaccines, multiple approaches are being explored to enhance the efficacy of currently available drugs and new domains like the role of epigenetic regulation, and their modulators are being researched extensively.There is no HPV-specific antiviral treatment for the infection. The screening and treatment of cervical precancerous lesions is an effective strategy to combat cervical cancer. The cervical precancerous lesions are mostly treated by invasive methods and ablative methods like burning/thermal ablation and cryotherapy-based destruction of abnormal tissue. The excision treatment is also prevalent, which involves large loop excision of the transformation zone (LLETZ) or cold knife excision (CKC) in women who are not eligible for ablative treatment ,182. TheThe miRNAs profoundly regulate gene expressions during carcinogenesis. Multiple clinical trials and studies have been conducted to study the role of miRNAs in their application as biomarkers or as therapeutic targets in treatment. miR-148b acts as a tumor suppressor during cervical cancer by inducing cell cycle arrest in the G1/S phase and apoptosis in a caspase 3-dependent manner, which makes it a prospective therapeutic approach for cervical carcinogenesis . A studyImmunotherapy has also been emerging therapeutics for HPV-associated cancers. E6 and E7 are potential targets for immunotherapy. Approaches like Anti-HPV protein mAbs, radioimmunotherapy, affibodies and affitoxins, single-chain antibodies (scFvs), nanobodies and T-cell-based therapies are novel mechanisms studied for the prevention of HPV-associated cancers. Native Anti-HPV protein monoclonal antibodies are reported to inhibit cervical carcinogenesis in mouse models. Monoclonal antibodies specifically targeting HPV E6 and E749-57 peptides lead to a significant reduction in tumor growth . RadioimDespite the advanced prevention strategies and intervention measures, screening facilities are not available for HPV-associated non-cervical cancers. In a systematic review and meta-analysis conducted by Balachandra et al., the utility and identification of blood-based biomarkers were reviewed . HPV-16 HPV infection has evolved to be the major cause of multiple malignancies. The malignancies share commonalities in pathways for malignant transformation, tumor biology, response to therapy and biomarkers, which can be helpful in designing proper strategies to combat increasing burden. Multiple treatment strategies are available, including the availability of prophylactic vaccines to the general population. However, vaccine coverage is limited to developed countries and high-income group populations due to high cost, vaccine hesitancy, lack of awareness, and still pending incorporation into universal vaccination programs in many countries. The current vaccines available are only effective if taken before exposure to the virus. However, owing to various disparities in income level, awareness and geographical conditions, it is not available to the majority of the population. WHO recommends that the vaccine be administered at ages 9–15 years. Despite this, there are still high rates of morbidity and incidence rates in various countries. Due to the global increase in HPV infection and even fewer people being administered the vaccine dose, it is imperative that countries prepare specific guidelines for the introduction of vaccines in their vaccination programs, making it cost-effective for high-risk groups and low-income populations. Awareness programs regarding sexually transmitted infections, vaccination coverage, exploring new technologies like miRNA-based therapies and developing strategic plans to implement policies and guidelines with respect to testing, affordable diagnosis and treatment may help in curbing the infection rate and progression in malignancies.