Long-term population-based studies have demonstrated that the risk of cervical cancer after conization for CIN3 treatment persists for at least 25 years, underscoring the need for careful follow ups and the importance of detecting residual disease after LEEP. Data from the literature show that positive-margin and post-treatment HPV persistence are predictors of residual disease. The management of these cases determines the use of a second LEEP or an accurate follow up, but the risk of overtreatment or of not treating an occult carcinoma exists. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a follow up (FU) only through the use of E6/E7 HPV mRNA search. This prognostic marker allowed us to identify women with residual disease (CIN2+) and treat them with a second LEEP. At the same time, it helped us identify E6/E7-mRNA-negative women as patients at low risk of progression, potentially avoiding further treatment and subjecting them to a follow up only.The risk of overtreatment or not treating an occult carcinoma exists in women at risk of residual disease after a LEEP excision for CIN3. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a FU only through an mRNA-detection test. In a population of 686 women undergoing a LEEP excision for CIN 3, we selected 285 women at risk of residual disease and subjected them to a search for E6/E7 mRNA HPV. The women with negative mRNA were subjected to a follow up, while the women with positive mRNA were subjected to a second LEEP. The histological examination of the second cone revealed 120 (85.7%) cases of residual disease in the mRNA-positive women: 40 cases of CIN2, 51 cases of CIN3, 11 cases of squamous microinvasive carcinoma, 7 cases of squamous carcinoma, 9 cases of AIS (adenocarcinoma in situ) and 2 cases of adenocarcinoma. Among the mRNA-negative women undergoing a follow up, there were only five cases of residual disease. During the follow-up period of about 6 years, we witnessed the regression of the residual disease and the elimination of the virus, just as predicted by the negative result of the mRNA test. Testing patients for E6/E7 mRNA allowed us to identify women with residual disease (CIN2+) and treat them appropriately. Papillomavirus infection is the most frequent sexually transmitted infection in the world . Its incThe removal of the cervical lesion as well as the entire squamocolumnar junction (SCJ) is the principle goal of LEEP (a large loop excision of the transformation zone). This procedure is considered the optimal treatment method for CIN3. Meta-analyses have shown that cone depth is associated with the risk of preterm birth; however, a more conservative treatment of CIN3 could potentially leave residual disease and infected tissue with the risk of progression causing a post-LEEP “positive margin” and “persistence of HPV infection”, respectively, both identified by the literature as risk factors for residual disease/lesion recurrence ,7.Long-term population studies have shown that the risk of cervical cancer after conization for the treatment of CIN3 persists for at least 25 years, underlining the need for a careful follow up and the importance of detecting the presence of residual disease, which is the diagnosis of CIN2+ at the first evaluation after conization .The “positive margin” was proposed as an accurate predictor for residual disease after conization. Generally, the positive margin is managed by a regular follow up or a second LEEP. Data from the literature report that almost half of the cases with a positive margin do not develop recurrent or residual disease, and that even patients with a negative margin may have residual disease . The risA meta-analysis by Arbyn et al. showed that HPV testing was more accurate than margin status in predicting residual disease, with an increased sensitivity (91% vs. 56%) and equivalent specificity (84%) .HPV testing has helped improve the diagnosis of post-LEEP residual disease; however, it shows a reduced specificity that limits the diagnostic accuracy . CurrentThe progression to cancer does not occur due to the presence of the virus but to the integration of the E6 and E7 genes and the overexpression of their transcripts; therefore, the demonstration of HPV E6/E7 transcripts in cervical samples may be more specific than HPV DNA testing alone.In 2010, we introduced into our clinical practice the use of the E6/E7 HPV mRNA test for the management of HPV-positive women. We also started using the test in the follow up of women treated with LEEP for CIN3. The high sensitivity and specificity make the mRNA test a valid diagnostic and prognostic marker ,15 that We performed a multicenter retrospective study; data from women who underwent cervical conization (LEEP) for CIN3 from January 2012 to December 2018 were collected into a dedicated database. We considered women who underwent LEEP for CIN3; had a margin status description of their histological examination; were positive for one or more of the following genotypes: 16, 18, 31, 33 and 45; and had performed an HPV test before and after the LEEP. All women were included in this study if they had undergone a second LEEP because of positive mRNA or were subject to a follow up because of negative mRNA, or if they had completed a 6-year follow up.Women who underwent LEEP for a histology other than CIN3, did not have follow-up data, were younger than 18 years old, had a positive pregnancy test or had a history of cervical cancer were excluded.All the women underwent an electrosurgical conical excision (conization) and/or diathermic loop surgical treatment (LEEP).Residual disease is the diagnosis of CIN2+ at the first post conization assessment; low-grade cervical lesions (LSIL/CIN1) were not considered as residual disease. The identification of the same type of HPV before and after the LEEP was considered HPV persistence.In the presence of positive margins, the first follow up is carried out three months after LEEP.The follow-up protocol included a pap test/repeated HPV test followed by a colposcopy every 6 months for two years and annually thereafter; if three subsequent cotests were negative, attendance occurred every three years.According to our protocol, women with positive margins and/or HPV persistence (285 women) were tested for E6/E7 HPV mRNA, women who tested positive underwent a second LEEP and negative women were followed up on. A histological examination of the second cone was reviewed by two pathologists.Written informed consent regarding the use of data for scientific purposes was obtained from all the participating patients.The University Hospital’s ethics committee waived the requirement of ethical approval and informed consent because the study used previously archived data.LEEP was performed with colposcopic guidance under local anesthesia in the clinic by experienced personnel; loops that were 20 mm wide and 12, 15 or 20 mm deep were used depending on the characteristics of the lesion and the conformity of the cervix. The resection margins were kept 2–3 mm beyond the lesion, and the completeness of the lesion removal was verified colposcopically. A histological examination of the cervical cone established the definitive histological diagnosis and evaluated the involvement of the cone margins. The margins of the cone were reported as positive if the distance between CIN2+ and the resection surface was <1 mm.After cytological sampling for HPV DNA, the samples were sent to the laboratory for DNA extraction  and viraHPV E6/E7 mRNA amplification and detection were performed with the PreTect HPV-Proofer real-time multiplex NASBA test, using a primer/probe PCR for HPV types 16, 18, 31, 33 and 45. The total DNA/RNA was extracted by using an Easy-Mag automatic extractor  women had positive margins and 512/686 (74.6%) had negative margins; 213 (31%) women had hr-HPV persistence and 473 (69%) were virus free .We tested 285 women at risk for residual disease (HPV-positive and/or margin-positive women) for mRNA HPV: 174 women had a positive margin, 111 women had a negative margin with viral persistence and 72 women had a positive margin but were negative for HPV infection .The 140 women who tested positive for E6/E7 HPV mRNA underwent a second LEEP excision, and the 145 negative women were followed up on.The residual disease among the 140 patients who underwent a second LEEP was 85.7%, and a histological examination of the second cone revealed 120 cases of residual disease: 40 cases of CIN2, 51 cases of CIN3, 11 cases of squamous microinvasive carcinoma, 7 cases of squamous carcinoma, 9 cases of AIS (adenocarcinoma in situ) and 2 cases of adenocarcinoma .Among the 145 women with a negative mRNA test result and subjected to a follow up, we had only five cases of residual disease: three cases of CIN3 and two cases of CIN2. p = 0.001  cases of residual disease in women with positive margins and 45 (40.5%) cases in women with negative margins, OR: 1.25 (CI 95% 0.8–2.0),  = 0.001 .p = 0.001. None of the HPV-negative and margin-negative women had residual disease. Genotype 16 had the highest persistence rate. As in other studies [Considering the viral status, in our study, the 6-month persistence rate was 31%; 110 51.6%) women with a persistent high-risk genotype had residual disease, and only 15 3.17%) HPV-negative women with positive margins had residual disease, OR = 4.06 (CI 95% 2.2–7.6), 1.6% wome% HPV-negPositive resection margins and viral persistence, particularly of genotype 16, after the primary LEEP were significant predictors of residual disease . The senWe had 125 (18.2%) cases of residual disease. In the literature, data on recurrence or residual disease are very variable as many studies do not clarify the definition of recurrence and residual disease and often do not distinguish between the term “relapse” and “residual disease”, using the generic term recurrent disease, leading to results that can have a vague interpretation. In our study, a woman with residual disease after LEEP still has a histological diagnosis of CIN2+, while recurrence entailed at least one negative examination between the primary LEEP and diagnosis of recurrence (CIN2+). In addition, in some studies, positive margins are defined as a histological diagnosis of CIN along with the margin of the LEEP sample, regardless of the CIN grade.Our results indicate that patient identification for a second LEEP based only on resection margin status would have resulted in the overtreatment of many young women and the insufficient treatment of a significant proportion of women; approximately 54% of the women in our series 94/174) with positive margins had no residual disease (CIN2+), while 45 (40.5%) women with negative margins had residual disease, which is compatible with the literature data that reported that 23–31% of patients with negative margins may have residual disease after LEEP and that 37–60% of patients with positive margins may have no residual disease 4/174 wit. A positAn occult microinvasive and invasive disease was observed in 24.2% of the residual disease cases, with 9 cases of invasive carcinoma and 20 cases of microinvasive carcinoma, all in women with a positive margin. The diagnosis of cervical cancer in women with positive margins varied between studies ,24; someOur data also support that a persistent HPV status after conization predicts residual disease more accurately than the margin status.p = 0.001. No patients with negative resection margins and negative HPV tests were shown to have residual disease. The sensitivity, specificity, PPV and NPV of the HPV test were higher than those for the resection margin, as confirmed by other authors [We had a viral persistence at 6 months of 31%; other authors reported lower 6-month HPV persistence rates, ranging from 14.3% to 21.5% . Our hig authors . The HPV authors . The tesWe used the E6/E7 mRNA search as a marker, subjecting only positive cases to a second LEEP. The mRNA test is used in clinical practice to study the ability of CIN progression or regression in HPV-positive women . CompareWith a high specificity and NPV, the HPV E6/E7 mRNA test compensates for the low specificity of DNA tests for the clinical detection of high-grade cervical lesions .In our study, it showed an excellent sensitivity (86%), excellent specificity (97%), PPV of 96% and NPV of 87.5%. These values make mRNA an excellent marker of progression, but also of regression in its negative form, reducing cases of overdiagnosis and consequent overtreatment. The positivity of the test identified the women to be subjected to a second LEEP, and the histological examination of the second cone showed 85.7% (120/140) of the cases of residual disease. Moreover, in 15 cases, the integrated viral genome was no longer visible to the DNA test but was detected by the E6/E7 mRNA test ,34; thisAmong the mRNA-negative women undergoing a follow up, there were only five cases of residual disease. During the follow-up period of about 6 years, we witnessed the regression of CIN2+ (three cases of CIN2 and two CIN3) and the clearance of the virus, just as predicted by the negative result of the mRNA test. Therefore, our results show that even in cases where residual disease (CIN2+) is present, it is not necessary to resort to a second LEEP but to be guided by markers capable of indicating the risk of the progression (mRNA+) or regression (mRNA−) of the lesion. In addition, women with negative HPV E6/E7 mRNA may increase the follow-up interval, reducing the rate of colposcopy and biopsy .This study is the first of our knowledge to evaluate the usefulness of HPV E6/E7 mRNA testing to identify women with residual disease to be subjected to a second LEEP.p = 0.001, of having a residual disease that progresses; the risk drops to 4.06 if the woman is hr HPV positive and to 1.25 if the woman has positive margins.In our study, a woman with a positive mRNA test has a risk of 168 , This study has several strengths, including a relatively large number of patients and a long-term follow-up (6 years), the multicenter design and the homogeneity of the patients included.The inclusion of a second histopathologic review of the second cone to confirm the diagnosis of residual disease further strengthens the validity of the results.An intrinsic limitation is the design of the retrospective study, as it generates a great deal of incomplete data; and, the NASBA technique used to search for E6/E7 mRNA referred only to five genotypes: 16, 18, 31, 33 and 45, which are the most oncogenes ,37. SearThe literature data show that margin status and post-treatment HPV testing are predictors of residual disease. To this now-accepted evidence, our study adds the usefulness of HPV mRNA testing as the most accurate predictive marker of residual disease, and we show that secondary treatments such as a second LEEP or hysterectomy would not be needed in a large number of cases. Testing patients for E6/E7 mRNA allowed us to identify women with residual disease (CIN2+) and treat them appropriately. At the same time, it helped us identify negative E6/E7 mRNA women at low risk of progression, potentially avoiding further treatment and subjecting them only to a follow up.


Background: There is a paucity of studies exploring women living with HIV’s (WLWH) experiences relating to human papillomavirus (HPV) self-sampling as cervical cancer (CC) screening approach, either at the clinic or at the home setting, using qualitative methods. Our study explored facilitators and barriers to HPV self-sampling as a CC screening approach among human immunodeficiency virus (HIV)-infected women, as supported by the new WHO guidelines of using the HPV test as a screening modality. Methods: The study was guided by the health promotion model (HPM), which helps individuals achieve higher levels of well-being. The phenomenology design was used to explore the deeper facilitators and barriers of women regarding self-sampling, either at home or in clinical settings, at Luweero District Hospital, Uganda. The in-depth interview (IDI) guide was translated from English to Luganda. Qualitative data analysis was guided by content analysis techniques. The transcripts were coded in   NVivo 20.7.0. The coded text was used to generate categories of analytically meaningful data that guided the formation of themes, the interpretation of results, and the final write-up. Results: WLWH were motivated to screen for HPV using the clinic-based approach because of perceived early diagnosis and treatment, visualization of the cervix, and free service, while reduced distance, privacy and the smooth sample collection kit were motivators for the home-based approach. A barrier that cut across the two HPV self-sampling approaches was a lack of knowledge about HPV. The barriers to clinic-based HPV self-sampling screening included lack of privacy, perceived painful procedures for visual inception under acetic acid (VIA), and fear of finding the disease. Stigma and discrimination were reported as the major barriers to the home-based HPV self-sampling approach. The major reasons why some WLWH refused to screen were fear of finding the disease, stress, and financial disruptions related to being diagnosed with CC disease. Conclusions: Therefore, early diagnosis for HPV and CC enhances clinic-based HPV self-sampling, while privacy enhances the home-based HPV self-sampling approach. However, fear of finding a disease and the lack of knowledge of HPV and CC hinders HPV self-sampling. Finally, designing pre- and post-testing counselling programs in HIV care is likely to increase the demand for HPV self-sampling. Cervical cancer (CC) is the most common cancer among Ugandan women . DespiteThe prevalence of human immunodeficiency virus (HIV) remains high at 7.6% among women in reproductive health . The WorPrevious studies indicated negative experiences among WLWH in relation to provider-led CC screening approaches, and these mainly included negative attitudes by health workers towards CC screening  and unfrHowever, there is a paucity of studies exploring WLWH’s experiences relating to HPV self-sampling as a CC screening approach, either at the clinic or in the home setting, using qualitative methods . The abiOur study explored facilitators and barriers to HPV self-sampling as a CC screening approach among HIV-infected women, as supported by the new WHO guidelines on using the HPV test as a screening modality. The study was conducted among women living with HIV in a rural setting who had access to HIV care. However, HPV self-sampling was relatively a new approach within this setting, where women are at risk of HPV infection due to multiple sexual partnerships. Therefore, understanding the dynamics of clinic-based vs home-based HPV self-sampling approaches was relevant, timely, significant, and interesting to explore. Hence, this study could be conducted in any HIV clinic supporting the integration of CC screening services with HIV care.The study was guided by the health promotion model (HPM) , which hThe phenomenology design was used to explore the deeper facilitators and barriers of women regarding self-sampling, either at home or in clinical settings, to elicit the barriers and facilitators to HPV screening in the Luweero District Hospital, Uganda. The paradigms underpinning the interpretations of the results included new feminist approaches and neoliberalism . Since tIn this study, women were selected from the randomized, controlled trial, where women were blinded and assigned either clinic- or home-based HPV self-sampling. The vignettes technique was used to educate women on HPV self-sampling. The demonstration focused on the use of the HPV sample collection kit and how it could be used at the clinic or at home. The midwife educated WLWH on HPV self-sampling and monitored them. The community linkages person (CLP) educated the women on the HPV self-sampling kit and self-sampling procedures. WLWH collected and returned the sample to the CLP. The clinic-based HPV DNA self-sampling approach was compared to the home-based HPV DNA screening approach to obtain a deeper understanding of the uptake and preferences of self-sampling in the clinical vs the home setting. In this study, the Qvintip® sampling device was used for sample collection by WLWH. It had an oval and smooth tip, which was preferred by WLWH, compared to the brush that was the standard in use by the HIV clinic.Information was gathered from key informants (KIIs) using in-depth interview (IDIs) guides. The KIIs included a program officer in the division of community health in the MoH, a cancer expert involved in cervical cancer at the Uganda Cancer Institute (UCI), and 4 health workers (HWs) at the Luweero District Hospital. At the district level, we interviewed the HIV clinic manager in charge of CC screening and the HIV clinic community linkage person. We interviewed 24 WLWH, all aged 25–49 years .The in-depth interview (IDI) guide was translated from English to Luganda, and the quality of the translation was assured through back-translation using a professional translator. Subsequently, the tools were pretested to eliminate ambiguities in the guides before the actual data collection. Despite the 3 research assistants (RAs) being experienced in conducting qualitative research, they were given additional study-specific training encapsulating the study aim, objectives, procedures, and ethical issues. Each interview took about 45 min to 1 h to be completed. Verbatim quotes were used to support the findings. The information gathered were related to the facilitators and barriers to the clinic- or home-based HPV self-sampling screening approaches. The key informants expressed their views on the experiences of CC screening approaches in the HIV clinic. At the inception, interview rapport was established, and women had the autonomy to decide whether to participate, freely express their views, or decline participation. The study was conducted and supervised by a team that included an expert on qualitative study methods who guided the study methods, as well as the analysis and interpretation of the findings.The recordings were transcribed in the local language (Luganda) and later translated into English by a professional translator whose native language was Luganda and who was proficient in the English language. This ensured that the meaning was not lost. Qualitative data from the in-depth interviews were transcribed verbatim before analysis. All transcripts were uploaded into NVivo 20.7.0  for analQualitative data analysis was guided by content analysis techniques. Initially, the study team read through printed transcripts and identified emerging themes. Using the coding approach proposed by Maxwell (1996), the team generated a list of relevant codes that led to the emerging themes . The traThe overall purposive sample was comprised of 30 participants. Of these, 24 were WLWH, 33% attained an upper primary level of education, and 33% attained secondary education. The majority (50%) of the WLWH were Catholics, and only three WLWH were Moslems. The number of WLWH for the HPV self-sampling approach was evenly distributed across home-based, clinic-based, and those that declined. The six other key informants were mainly HPV and CC service providers.Data analysis produced mainly three themes  and subthemes . Participants further proposed some interventions that could mitigate the impediments related to HPV self-sampling approaches. The key suggestions were mainly: considering HPV screening pre- and post-testing counseling for women attending ART clinics; improving the laboratory capacity and reducing the turnaround time for the HPV test result; and streamlining HPV logistics requisition within the National Medical Stores (NMS) supply chain. Participants further highlighted that the HPV/CC screening staff should be incentivized so that they are motivated to routinely screen WLWH, as summarized below .a.Motivators for clinic-based HPV self-sampling approachParticipants identified perceived early free diagnosis and treatment, as well as education on the risks of HPV and the benefits of HPV testing, as the motivators for the clinic-based HPV self-sampling approach.For clinic-based HPV screening, participants mentioned perceived early diagnosis and treatment of HPV as benefits of being screened at the clinic by a skilled health worker (HW), where medical instruments are housed. WLWH also believed that the HW would immediately diagnose the disease and provide treatment through the thermocoagulation process. In circumstances where a woman was found with suspicious lesions, they would be referred for further management.The health workers (HWs) are capable and all the instruments available. The health workers are skilled, even if they found you complicated, they know where to refer you very fast to test for whatever they want to know. WLWH are likely to come to the clinic to screen for HPV and CC because of perceived early diagnosis and treatment”.“P1 WLWHThe key informants also mentioned being educated on HPV, the risks of HPV infection, and the benefits of HPV and VIA screening as critical motivators for the clinic-based approach. The fact that being on-site at the clinic enabled health workers to take pictures of the cervix and educate women on the state of their cervix was seen as a key motivator for clinic-based self-sampling. WLWH, through visualization and education, were able to receive knowledge on HPV and CC, as well as to return for the next appointment for screening.Most of the women usually accept to screen at the clinic because they get feedback, especially those already having signs of CC. I usually take a picture of the cervix upon applying VIA and share this image with WLWH. I educate the women about HPV and CC using the images of their cervix…… WLWH are motivated to go for further management if referred because they fear progression into advanced disease”.“P26 HWWLWH also obtained education if they had a family history of CC, where a relative or friend underwent HPV testing and CC screening or was confirmed to have CC disease. This was further evident in the quote below;Recently one of my nieces sent us an audio telling us that her cervix was sick, and when diagnosed she was found with cancer of the cervix, yet she has never given birth to any child, so she was going for an operation, so there you also go and encourage other women to test because prevention is better than cure, though not everyone knows it”.“P9 WLWHb.Motivators for home-based HPV self-sampling approachThe participants largely identified privacy during the HPV self-sampling procedure, reduced distance to return the collected sample, and a soothing HPV collection kit during the vaginal sample collection procedure as key motivators for the home-based HPV self-sampling approach. Participants echoed that the home-based approach offered privacy during the HPV DNA self-sampling procedure. WLWH mentioned that collecting the sample from home was easy and fast, as it was conducted conveniently in a private place within their homes. It was also easy to follow the sample collection procedures described by the HWs.It is good because it is private, no opening up your legs for another person as they tell us to open your legs wide when being screened by a midwife at the CC clinic.”“P10 WLWHThe home-based HPV self-sampling approach reduced the distance traveled to be screened, as WLWH would pick HPV sample collection kits from the community expert clients, who were community linkage representatives (CLRs) within the community. The WLWH returned the HPV sample in its buffer to the CLRs. The community linkage representative was a selected member from the ART clinic with prior training and support in the triage of HIV patients, and they resided within the same community for the selected group of ART clients. Thus, these CLRs facilitated the distribution of HPV kits during the ART community outreach clinics and were the key contact persons for receiving and transporting the self-collected sample to the hospital laboratory. As a result of the transportation of the kits by the CLRs, sample transportation was made easy, and transport costs were reduced, as the CLRs brought the kits to the lab.When women use the clinic-based HPV self-sampling approach, they usually travel a distance close to 60 kms. When samples are self-collected from and returned to the designated expert client within the community, are within reach of at least 0–10 km. The distance is easy to manoeuvre with to return the kits which are transported to the lab by the expert client.”“P25 HWThe WLWH who were in the home-based arm also mentioned that the Qvintip HPV DNA kit  was a faa.All-encompassing barriers to HPV screening approachThe major barriers to HPV self-sampling using the clinic- and the home-based approaches were a lack of knowledge about HPV infection and CC disease, as well as fears related to poverty. The majority of WLWH who declined HPV self-sampling were not knowledgeable about the HPV infection and its related risks of causing CC among women. Even with group education, they preferred to be given more time to learn about HPV before they would consider being screened.Women don’t make CC screening a priority, for example, those women who are always digging will only be thinking about digging and may not make their health a priority that way they will not come for testing, furthermore education status, you know if you are not educated and not knowing about the disease and its danger, they will not come for testing.”“P8 WLWHI don’t know anything, I just hear about the word cancer of the cervix, I don’t know its signs.”“…P14 WLWHPoverty was another challenge that prevented women from coming to the clinic, as they were afraid of incurring expenses of treatment should they be found with advanced CC disease. Further still, the clinic-based approach disrupted their family’s financial flow in situations where they were diagnosed with suspicious lesions, with the fear of finding the disease and the painful procedures being viewed as additional deterrents.because cervical cancer is very expensive to treat. If a person cannot afford to buy treatment, that means they will need family support, which will disorganize the family finances.”“…P5 WLWHWhen you are very sick with a disease like cervical cancer, you may lose yourself to thoughts and there you will stop working, you get disorganized even your family members as they try to plan ways of saving your life, spend a lot of time and money.”“…P8 WLWHThe failure to return the kits due to a lack of transportation was another barrier to the home-based approach, including having to travel long distances to return them to the community expert clients. Despite the community expert clients living within the communities, the distances between them were sometimes long, with additional transport costs for women to return the self-collected sample.The distance within the communities is still long, like when you would go there somebody would tell you like Kikyusa yet Kikyusa is very wide with quite several villages far apart. Therefore, the distance between the woman and the expert client sometimes can be more than 10 km. The women may not have the transport fares to return the kit to the expert client.”“27 HWb.Clinic-based HPV self-sampling barriersAt the clinic, the women reported that they faced the challenge of the intrusion of privacy. Hasty collection of the samples to create space for peers, as there was one room provided for the self-sampling approach at the clinic, was an important barrier. WLWH stated that screening with VIA pushed them to expose their private parts and made the entire screening approach uncomfortable.It is very scary as the Health workers insert those instruments in you they pierce you, and you suffer pain for about four days, HPV self-sampling is very simple and not painful.”“P9 WLWHc.Home-based HPV self-sampling barriersStigma and discrimination within the home-based approach were large concerns of the participants, as they were afraid to be identified as women living within the community.There is a fear of discrimination and shyness because not everyone can keep a secret if I am diagnosed with cervical cancer. The lack of Family support or fear of being discriminated against stops me from seeking cancer screening services as well as collecting the sample from home.”“P13 WLWHThis study aimed to explore the facilitators and barriers to HPV self-sampling approaches among HIV-infected women attending a rural ART clinic in Uganda. We deductively derived themes from facilitators for HPV self-sampling approaches, barriers to HPV self-sampling, and suggestions for improving HPV self-sampling among WLWH. In this discussion, we focused on findings relating to facilitators, barriers, and suggestions that would deepen our understanding of issues relating to HPV self-sampling among HIV-infected women.In our study, most of the respondents were Catholics by religious domination, and an equal number of participants either obtained a primary or secondary level of education. There is high dominancy in the Catholic religion of primary and secondary levels of education within Uganda, as indicated in the Uganda Demography and Health Survey 2016 . Our disThe findings from this work mainly focused on WLWH who were motivated to screen for HPV and CC at the clinic because of the perceived benefits of early diagnosis and treatment. Perceived benefits of the clinic-based HPV self-sampling were mainly considered to be the visualization of the cervix and free service. An example would be the findings in other studies, where HIV-infected women were motivated to screen for CC at the clinic , and allThis finding was critical, similar to a systematic review conducted in Sub-Saharan Africa, where women preferred home-based HPV self-sampling because of the privacy and convenience when collecting the sample . The homThe other major theme that emerged was the barriers to HPV self-sampling approaches. Barriers that cut across the two HPV self-sampling approaches were a lack of knowledge of HPV and the perceived disruption of financial flow in case CC disease was diagnosed. The barriers specific to clinic-based HPV self-sampling screening included the lack of privacy, perceived painful procedures for VIA, and a fear of finding the disease. Stigma and discrimination were reported as the major barriers to the home-based HPV self-sampling approach. Further still, the major reasons why some WLWH refused to screen were fear of finding the disease, stress, and financial disruptions related to being diagnosed with CC disease.The other major themes that emerged were the barriers to HPV self-sampling approaches, with a lack of knowledge of HPV and the perceived disruption of financial flow in case CC disease was diagnosed being the overarching barriers. This finding was congruent with the study conducted in Ethiopia, where a lack of knowledge about cervical cancer and screening and a lack of health education on cervical cancer and HPV-based screening hindered HPV self-sampling . There wWomen in a similar social situation but who were HIV-negative did not prefer to be screened at clinics because of a lack of privacy . The barFurther still, the major reasons why some WLWH completely refused to screen were fear of finding the disease, stress, and financial disruptions related to being diagnosed with CC disease. The decline in HPV self-sampling could be attributed to religion in this study, mainly with Muslims and Anglicans. Reasons for refusal were consistent with findings from previous studies, where the fear of finding the disease and being Moslem were the main reasons for refusing to screen for HPV and CC ,36,37,38Despite the identified barriers, key informants proposed some interventions to mitigate the impediments related to HPV self-sampling approaches. The key suggestions were mainly: considering HPV screening pre- and post-testing counseling for women attending ART clinics; improving the laboratory capacity and reducing the turnaround time for the HPV test results; and streamlining HPV logistics requisition within the National Medical Stores (NMS) supply chain.a.Suggestions for clinic-based improvementsCounselling of patients within ART clinics remained amongst the key suggestions for improving the clinic-based approach to HPV self-screening. The strengthening of the lab capacity to shorten the turnaround time for HPV test results was an additional suggestion. The screening team mentioned that there was a need to streamline the cycle for the logistics distribution of VIA and HPV DNA reagents such that shortages would be controlled. Economically, it was suggested to provide extra financial support to the screening staff in the clinic to motivate them to routinely screen women for HPV. In terms of prevention, a solution proposed for reducing the risk of HPV was to consider vaccination for HPV-negative women living with HIV.b.Suggestions for home/community-based improvementsParticipants proposed the formation of community ART support groups, including a triage support system and selection criteria for community ART experts who support the community and reside in the area.There is a lack of information on the feasibility or effectiveness of the above interventions. Thus, more studies are needed to understand the potential value of these suggestions. It was highlighted that the HPV/CC screening staff should be incentivized so that they are motivated to routinely screen WLWH. Digital financial incentivization was studied in other programs, such as immunization , but theThe study was prone to social desirability bias, and we did not verify the authenticity of the views shared. However, to mitigate the risk of social desirability, the objectives of the study were well explained, and we invested in building rapport at the beginning of the study.This was mainly a qualitative study where views were collected from a small, purposively selected sample and might not provide a general representation of all WLWH in rural areas.We, therefore, conclude that perceived early diagnosis for HPV and CC enhances clinic-based HPV self-sampling, while privacy enhances WLHW’s preference for the home-based HPV self-sampling approach. However, fear of finding a disease and the lack of knowledge of HPV and CC hinders HPV self-sampling. Finally, designing pre- and post-testing counseling programs in HIV care is likely to increase the demand for HPV self-sampling. It will also be required for HIV clinics to create safe spaces at ART clinics for clinic-based HPV self-sampling. There is a need to design a clear strategy for home-based HPV self-sampling while leveraging ART community linkage systems.


Objective To determine the frequency of sexually transmitted infections (STIs) in asymptomatic women and the association of STIs with cervical intraepithelial neoplasia (CIN).Methods A cross-sectional study was performed, enrolling women examined in a general gynecology clinic and in a colposcopy referral center from October 2014 to October 2015. The colposcopy group consisted of 71 women, and the general gynecology group consisted of 55 women. Cervical samples were collected for cervical cytology and a multiplex real-time polymerase chain reaction (PCR) was developed to detect human papillomavirus (HPV) and the STIs caused by the following microorganisms: Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Neisseria gonorrhoeae. A multivariate analysis was performed by logistic regression, considering the significance level of 0.05.Results The general frequency of STIs was: 46.8% (HPV); 27.8% (C. trachomatis); 28.6% ; 0.8% (M. hominis); 4.8% ; and 4.8% (N. gonorrhoeae). The significant risk factors for CIN were: HPV infection ; C. trachomatis ; M. genitalium ; and HPV and C. trachomatis coinfection . After the multivariate analysis, a significant association was found between HPV and CIN ; and between C. trachomatis and CIN .Conclusion The frequency of STIs was high in asymptomatic patients. Infections by HPV and C. trachomatis were independently associated with the presence of CIN. The high frequency of STIs in asymptomatic women suggests the need for routine screening of these infections. Cervical carcinoma is the third most common cancer among women worldwide, and the highest number of cases is being detected in women from developing countries. The carcinogenic human papillomavirus (HPV), a highly prevalent sexually transmitted infection (STI), is a necessary cause to the development of cervical intraepithelial neoplasia (CIN), and it has a central role in the etiology of cervical carcinoma.Chlamydia trachomatis as a cofactor for the development of CIN, as well as other significant cell abnormalities in women with a history of HPV infection.C. trachomatis. The incidence rate is increasing in developed countries, and according to the World Health Organization (WHO), more than 1 million STIs are contracted every day worldwide.Many studies consider C. trachomatis, and 78 million people with Neisseria gonorrhoeae. The high prevalence of C. trachomatis and N. gonorrhoeae, including significant rates of asymptomatic infections (50–80% of men and women), and the potential for severe complications are important factors that justify the routine screening of these bacteria.It is estimated that each year 131 million people are infected with C. trachomatis, N. gonorrhoeae, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium are frequently asymptomatic.The widespread prevalence of STIs, and the public health costs associated with the difficult diagnosis of these infections have led to the development of fast and reliable methods for diagnosing STIs.The objective of the present study was to identify the frequency of STIs, associated or not with HPV, and to determine their possible association with CIN among asymptomatic women.The study was approved by the Ethics in Research Committee of Instituto de Educação e Pesquisa da Santa Casa de Belo Horizonte, Brazil (CAAE-0544.0.000), and registered in the National Ethics in Research Commission .This is a cross-sectional study that involved 126 women who live in Belo Horizonte, state of Minas Gerais, Brazil, during the period between March 1st, 2014, and September 30th, 2015. The patients were divided into 2 groups: Group 1, composed of 55 women who presented at a general gynecology outpatient clinic (low risk of STI) at Centro de Especialidades Médicas, Santa Casa de Belo Horizonte; and Group 2, composed of 71 women that were referred to a colposcopy clinic (high risk of STI) at Ambulatório de Patologia Cervical of the Centro de Especialidades Médicas, Santa Casa de Belo Horizonte. Among the 71 patients evaluated in the colposcopy clinic, 59 (84%) had abnormal cytology, 41 (59%) underwent a biopsy, 33 (46.5%) presented CIN, and 19 (27%) were CIN 2-3. All patients were asymptomatic for condyloma, abdominal pain, and abnormal vaginal discharge. The exclusion criteria were: pregnancy or postpartum periods, previous hysterectomy, and vaginal bleeding. All of the participants voluntarily agreed to provide a sample for a Pap smear, and for HPV DNA and STIs detection, and signed an informed consent form.Cervical cytology was performed in all patients. Samples were collected using an Ayre spatula and cytobrush  for Pap smear collection. The results were reported according to the 2001 Bethesda System.The DNA was extracted from clinical samples as described by Sambrook and Gething.The detection of HPV was performed by multiplex real-time polymerase chain reaction (M-qPCR) using the general primers GP5 + /GP6+ N. gonorrhoeae, C. trachomatis, U. urealyticum, M. hominis, and M. genitalium. The β-actin gene was used as an internal control to ensure the quality of the extracted DNA. Positive STI controls were used in all M-qPCRs, as well as a negative control. All reactions were performed in universal cycling conditions with TaqMan Universal Master Mix buffer in the 7500 Real-Time PCR System . The assays were performed in duplicate for all genes, and the results were analyzed using the 7500 Fast Software, version 2.1 . The samples were analyzed at Instituto de Educação e Pesquisa da Santa Casa de Belo Horizonte, in a partnership with Laboratório Hermes Pardini.The detection of others STIs was performed by M-qPCR with TaqMan  probes using specific assays to detect simultaneously p < 0.05. All statistical analyses were performed using SPSS Statistics for Windows, version 17.0 .The two-sided Fisher exact test for the 2 × 2 contingency table was used to evaluate the statistical significance between different groups . Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the association of HPV, non-HPV, and STIs with CIN. Variables that exhibited statistical significance at the 0.2 level were included in the multivariate analysis using a logistic regression model adjusted by potential confounders. Statistical significance was defined as The characteristics of the patients in each group, such as age, number of partners, smoking habits, early sexual activity, and contraception are shown in M. genitalium, 28.6%; C. trachomatis, 27.8%; U. urealyticum, 4.8%; N. gonorrhoeae, 4.8%; and M. hominis, 0.8%. p = 0.003). No statistical differences between the analyzed groups were observed with the other STIs.The frequency of STIs, independently of CIN occurrence, were: HPV, 46.8%; p = 0.024), C. trachomatis and CIN , and M. genitalium and CIN . No significant associations were observed with the other STIs . A significant association between HPV and CIN  and between C. trachomatis and CIN  was observed.Finally, a multivariate analysis was performed to select the final predictor variables from the univariate model , besides the detection of HPV DNA by conventional PCR.The aim of the present study was to evaluate the frequency of STIs in asymptomatic patients, using M-qPCR to identify five genital infections: Molecular tests by M-qPCR represent the first line option for the diagnosis and screening of STIs in developed countries.M. genitalium (28.6%) and C. trachomatis (27.8%). Among 126 patients, 66% were infected with at least one STI, and some were simultaneously infected by 2, 3, and even 4 pathogens. In similar investigations, a high prevalence of HPV (46%), C. trachomatis (21%), N. gonorrhoeae (5%) and Gardnerella vaginalis (39%) was reported in symptomatic and asymptomatic groups of women, suggesting that, belonging or not to a high-risk, group, all women should be screened and treated for STIs.The present study showed that even in asymptomatic women, belonging or not to a high-risk group, there is a high frequency of STIs, especially HPV (46.8%), C. trachomatis, a larger frequency of infection was found than the one reported in the current literature (27.8%). In general, women from developing countries present a higher prevalence of C. trachomatis infection, but not as high as that found in the present study. Some authors have reported prevalence values of C. trachomatis ranging from 5 to 22%, reaching 41% among female adolescents.C. trachomatis has presented a frequency ranging from 2 to 10% in the general population, and from 5 to 20% among adolescent females.Regarding M. genitalium was found, and it was greater than the literature reports.M. genitalium around the world are important in public health, especially in countries where there is no data on the affected population. Currently, there iis a suggestion to include the routine screening for this STI, considering the possible damage for women's health related to the high prevalence in asymptomatic women. The association of M. genitalium with CIN is yet to be established in the literature because this STI has been investigated more recently with the use of PCR for multiple pathogens. At the same time, studies have shown the association of several STIs with CIN without evaluating the isolated association of M. genitalium with the cervical neoplasia.Similarly, a high frequency (28.6%) of Neisseria gonorrhoeae was found in 4.8% of the women in the present study, a frequency similar to that reported in the literature, with frequencies ranging from 3 to 12%.It is known that the presence of HPV is necessary and one of the most important factors for the development of cervical cancer. However, it is also recognized that the role of other different risk factors in association with HPV is crucial in cervical carcinogenesis. Several studies have shown that factors such as smoking, multiparity, prolonged use of contraceptives, and other STIs can triple the risk of development of precancerous lesions, or even of cancer, among women infected with oncogenic types of HPV 16 and 18.C. trachomatis reached 15% (p = 0.023). Some authors have found a high prevalence of coinfection by HPV and C. trachomatis in patients with CIN 2-3, suggesting that these infections need to be investigated and treated in young women.C. trachomatis in the cervical epithelium may be defined as a gateway, enabling the HPV to acess the basal layer of the epithelium, increasing the viral load, interacting with HPV high-risk types, and modulating the host immune response by inhibiting the apoptosis process.Epithelial cells play an important role in the induction of an innate immune response in the female genital tract. These cells lined on the mucosal surfaces not only act as a physical barrier, but also actively participate in the secretion of antimicrobial substances and immune factors such as defensins, lactoferrin, and lysozyme. It is believed that an STI can reduce the resolution of HPV infection, with an induction of a pattern of innate and acquired immune response, especially humoral immunity.C. trachomatis and CIN. We suggest a discussion about the opportunity of including these STIs in a routine gynecological screening, using biomolecular methods that could detect multiple infections simultaneously, including HPV infection, to avoid the development of CIN.Our study demonstrated a high frequency of STIs in asymptomatic women, confirming the association of HPV with CIN, and an unexpected significant association between


ZSCAN12 and GYPC via real‐time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep‐based liquid cytology samples. Here, we investigated whether the WID‐qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath‐based hospital‐cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99  with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital‐cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98‐1) with a sensitivity and specificity of 100% and 82.5% for the WID‐qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID‐qEC test detects both endometrial and cervical cancer with high accuracy.The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator‐independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID‐qEC test, which assesses DNA methylation of  What's new?While abnormal vaginal bleeding is a presenting symptom of endometrial and cervical cancers, only a small proportion of women who present with vaginal bleeding have endometrial or cervical cancer. Currently, the tests used to triage women with abnormal bleeding, such as ultrasound or cytology, are subjective and have modest accuracy. Here, the authors demonstrate that a real‐time PCR‐based test, which assesses DNA methylation at three gene regions using a cervical or vaginal sample, is able to identify 100% of women who have cervical or endometrial cancer with a high specificity (>80%), irrespective of the sample collection system. AUCarea under the curveCAHcomplex atypical hyperplasiaCIconfidence intervalCINcervical intraepithelial neoplasiaHPVhuman papilloma virusPMRpercentage of fully methylated referenceROCreceiver operating characteristic1Endometrial cancer is amongst the cancers with the steepest rise in incidence.In addition to conventional cytology as the primary test method for cervical screening, the application of liquid‐based cytology, utilizing either ThinPrep or SurePath systems, has been established in many countries with organized cervical cancer screening programs.ZSCAN12 and GYPC genes.Recently, we reported the WID‐qEC test, a real‐time PCR‐based test assessing methylated alleles of regions within the Here, we have employed a case/control and a hospital‐based cohort study to assess whether the WID‐qEC test (a) is also able to detect cervical cancer, (b) is also applicable for SurePath samples utilizing the same threshold as defined in our previous studies, (c) is superior to cytology and (d) retains a low false‐positive rate when assessed within a hospital‐based cohort.2Case/control setting: Cervical smear samples collected in ThinPrep from women with cervical cancer  and matched cancer‐free control women . These samples were collected within the FORECEE study Cervical smear samples from a hospital‐based cohort: Women who attended the gynecology department at the general district hospital in Hall in Tirol were invited to provide a written consent that their sample (collected exactly as described above but in SurePath), surplus to cytological assessment and human papilloma virus (HPV) testing can be utilized for research. A written informed consent was obtained from a total of 330 women. Cytological assessment and HPV testing were carried out in 329 women, of which 326 had sufficient residual sample available for DNA extraction. A total of 6/330 women were eventually diagnosed with a cancer . The remaining 320/330 were diagnosed with preneoplastic lesions , had cancers in the past but were currently disease‐free, or had benign conditions . In short, cervical DNA was extracted using the Mag‐Bind Blood and Tissue DNA HDQ 96 Kit  as per the manufacturer's protocol, but with the addition of a heat‐incubation step at 100°C for 40 minutes to ensure formalin‐induced DNA‐protein crosslink‐reversal. DNA was normalized and bisulfite modified using the EZ‐96 DNA Methylation‐Lightning Kit  as per the manufacturer's protocol. Bisulfite modified DNA was amplified using the ×1 Luna Universal Probe qPCR Master Mix  and primer‐probe sets as described.ZSCAN12 and GYPC (two independent regions) genes as well as the reference gene COL2A1, were performed in technical duplicates. PCR reactions were run on the QuantStudio 7 Pro (Applied Biosystems) and results further extracted via the Design and Analysis Software 2.5.0 (Applied Biosystems). The PMR molecules at the target locus were standardized using an R script, dividing the TARGET:COL2A1 input amount ratio (derived using the COL2A1 standard curve) of a sample by the TARGET:COL2A1 input amount ratio of gBlocks Gene Fragments DNA and multiplying by 100.DNA methylation‐specific, quantitative real‐time PCR (MethyLight) analysis was performed as previously described.All statistical analyses were carried out in R version 4.1.2 (1 November 2021). Receiver operating characteristic curves, areas under the curve and corresponding 95% confidence intervals (CIs) were generated using the pROC package, version 1.18.0. Sensitivity and specificity including 95% CIs were calculated using the bdpv package, version 1.3. Cross tabulation and chi‐square test were performed using the sjPlot package, version 2.8.11.3The WID‐qEC receiver operating characteristic (ROC) area under the curve (AUC) to distinguish cervical cancer cases and controls in the case/control setting (n = 51) was 0.99 (95% CI: 0.97‐1.00) Figure . ApplyinAmongst the hospital‐based cohort (n = 330), the ROC AUC distinguishing endometrial or cervical cancers from all controls (including CIN2/CIN3) was 0.99  and 1 woman was suspicious for endometrial cancer  but refused procedures to obtain a histological diagnosis. HPV infections did not seem to drive false positive WID‐qEC results: Amongst the 298 CIN2/3 negative controls, 1/46 (2.2%) WID‐qEC false positive and 11/252 (4.4%) WID‐qEC true negative women tested positive for HPV16. None of the CIN2/3 negative controls were HPV18 positive and 4/46 (8.7%) WID‐qEC false positive and 26/252 (10.3%) WID‐qEC true negative cases were positive for other oncogenic HPV strains . In addition, none of the false positive women had previously received radiotherapy.Amongst the 4/6 cytology false negative cancer cases, three women were subsequently diagnosed with endometrial cancer , and one woman suffered from an adenocarcinoma of the cervical canal (PAP IIIG).Our previous findings highlighted that the WID‐qEC detects endometrial cancer across a variety of sampling settings, including self‐sampling. In accordance with these prior findings, our data indicate that this new PCR‐based test is robust and outperforms cytology to detect both cancers arising from the uterus, endometrial and cervical, irrespective of whether the ThinPrep or SurePath system is utilized for liquid‐based cytology sampling. Of note, the ThinPrep system may be the preferred one over SurePath due to the absence of formalin in the PreservCyt media which allows for easier sample processing. Our data also confirm the low sensitivity of cytology to detect endometrial cancer.Overall, our current results, in conjunction with recently published data,Lena Schreiberhuber: Conceptualization; Formal analysis; Investigation; Methodology; Writing—original draft; Writing—review and editing. Chiara Herzog: Conceptualization; Formal analysis; Writing—review and editing. Charlotte D. Vavourakis: Writing—review and editing. Elisa Redl: Investigation; Methodology; Writing—review and editing. Christine Kastner: Investigation; Methodology; Writing—review and editing. Allison Jones: Investigation; Methodology; Writing—review and editing. Iona Evans: Investigation; Methodology; Writing—review and editing. Michal Zikan: Methodology; Writing—review and editing. David Cibula: Methodology; Writing—review and editing. Peter Widschwendter: Conceptualization; Methodology; Writing—review and editing. Karin Pfau: Methodology; Writing—review and editing. Barbara Math: Investigation; Methodology; Writing—review and editing. Martin Seewald: Investigation; Methodology; Writing—review and editing. Sylvain Amory: Investigation; Methodology; Writing—review and editing. Peter Obrist: Conceptualization; Investigation; Methodology; Writing—review and editing. Martin Widschwendter: Conceptualization; Formal analysis; Writing—original draft; Writing—review and editing. The work reported in the article has been performed by the authors, unless clearly specified otherwise in the text.https://eveappeal.org.uk/).Our study was funded by the European Union's Horizon 2020 European Research Council Program, H2020 BRCA‐ERC under Grant Agreement No. 742432 as well as the Land Tirol and the charity The Eve Appeal  program, which has ethical approval from the UK Health Research Authority (REC 14/LO/1633) and all other contributing centers. The hospital‐based cohort study has received ethical approval from the ethical committee of the Medical University Innsbruck . All volunteers provided a written informed consent.


Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2 (HSV), Mycoplasma spp., molluscum contagiosum virus (MCV), Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. The subsequent statistical analysis aimed to reveal correlations between HPV genotypes and the identified pathogens. Results: Of the participants, 72.1% (n = 294) tested positive for HPV genotypes. HR-HPV (high-risk HPV) genotypes comprised 51 (8.1%), 66 (7.1%), and 58 (6.1%). Haemophilus spp., Ureaplasma spp., Candida spp., Staphylococcus aureus, and Mycoplasma spp. frequently co-occurred with HPV infection (p < 0.05). Gender-based variations were notorious for Ureaplasma spp., Mycoplasma spp., and MCV (p < 0.05). Coinfections were prevalent (43.9%), with a positive HPV result elevating the risk for Trichomonas vaginalis, Mycoplasma spp., Staphylococcus aureus, HSV, and MCV . HPV 16 correlated with HSV and Ureaplasma spp., while HPV 6 was linked with HSV and MCV (p < 0.05). Conclusions: This screening strategy uncovered significant coinfections and associations between HPV genotypes and pathogens, underscoring the importance of routine screening to explore clinical implications in urogenital health.Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) worldwide, with popular screening methods including the Papanicolaou test and HPV genotyping. However, in clinical practice, coinfections with other pathogens are often underestimated. Therefore, our study aims to describe the prevalence of STIs and vaginosis in urogenital samples from patients who had been tested exclusively for HPV genotyping. Methods: This analytical, prospective, cross-sectional study included 408 males and females. Eligible participants had positive and negative HPV genotyping test results and agreed to early detection or had HPV antecedents. They provided the same urogenital samples used for HPV detection and, through our multiplex in-house PCR assay, we screened for  Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the world and, due to its relationship with oncogenic processes, PAP tests or HPV genotype identification are present in routine clinical practice. Much evidence supports the theory that infection at urogenital sites increases the risk of acquiring other pathogens and developing diseases, either by predisposing the microenvironment or complicating or increasing HPV-induced carcinogenesis, causing concerning clinical complications ,2. HowevThe detection of STIs and other pathogenic microorganisms, such as HPV and the bacterium responsible for bacterial vaginosis, is crucial to public health and patient wellbeing. However, in clinical practice, simultaneous testing for these pathogens is often underestimated. This lack of attention given to simultaneous detection can hinder the precise identification of coinfections, which, in turn, can adversely affect the diagnosis, treatment, and prevention of these infections.Molecular detection methods based on molecular biology and polymerase chain reaction (PCR) have emerged as an essential tool for screening for multiple infections. These advanced techniques enable the identification of specific genetic material from different pathogens in a single sample, simplifying the detection process and significantly increasing the accuracy. Furthermore, molecular methods offer additional advantages, such as a greater sensitivity and specificity, the ability to identify specific viral or bacterial strains, and the early detection of infections that may be asymptomatic in their initial stages . In partChlamydia trachomatis, Neisseria gonorrhoreae, Mycoplasmas, Ureaplasmas, and HPV is routinely performed; nevertheless, in some cases, the presence of other viruses, like molluscum contagiosum virus (MCV), which has been detected in patients with positive and negative HPV test results , and 2 μL (100 ng/μL) of total nucleic acid extraction. Once the single target PCR system succeeded, we performed the in-house multiplex PCR assay, mixing the primers for the Complementary STI Panel , respectively. The positive samples were analyzed by sequencing at Macrogen Inc. . The sequences were blasted against available sequences in the GenBank to identify and corroborate the microorganism.Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, HSV, Mycoplasma spp., MCV, Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. in the same sample used to detect HPV genotypes.Finally, the combination of Basic and Complementary STI Panels was suitable to identify 2 test examined the relationship between HPV genotypes and infections with microorganisms that cause STIs and/or vaginosis. p < 0.05 was chosen as the statistical significance threshold. Additionally, a conditional logistic regression was carried out to evaluate the chance of coinfection in the presence of a positive HPV test and to provide odds ratios (ORs) with 95% confidence intervals.IBM SPSS version 28 was used for our descriptive and inferential statistics . Quantitative data with a normal distribution were described as mean SD (standard deviation), while qualitative data were expressed as frequencies and percentages. The chiData from 408 participants were analyzed. Initially, we analyzed the anthropometric and clinical characteristics of the patients. We found that the average age of the patients was 30.2 ± 10.7 years; 53.9% were female and 46.1% were male. The main reasons for the clinical analysis were early detection (90.9%), condylomas (3.2%), and HPV history (2.7%) .We investigated the frequency of high- and low-risk HPV genotypes in both sexes. The overall prevalence of high-risk (HR) HPV was 33.3%, and low-risk (LR) HPV was 37.5% in both men and women . We founp < 0.01)  .For the numerous detections of the microorganisms that cause STI and vaginosis, two internal STI panels (Basic and Complementary Panels) based on multiplex PCR were used. The panels were validated previously in the laboratory, evaluating the robustness and reproducibility of the results. Haemophilus spp. (32.4%), Ureaplasma spp. (24.8%), Candida spp. (11.8%), Staphylococcus aureus (7.1%), and Mycoplasma spp. (6.9%) as the most frequently associated pathogens with HPV in our patients. Among women, the most common pathogens were Ureaplasma spp. (15.9%), Haemophilus spp. (15.4%), and Mycoplasma spp. (5.6%), while among men, they were Haemophilus spp. (16.9%), Ureaplasma spp. (8.8%), and Candida spp. (6.6%)  with the most common etiological agents of STI in both men and women. We identified . (6.6%) b.Ureaplasma spp. (p = 0.015), Mycoplasma spp. (p = 0.002), and MCV (p = 0.023)  . Specifin in men b.The median age of patients with a positive HPV result was 34 years, and for those with a negative HPV, the result was 33 years. The median age of cases that tested positive for STI-causing bacteria was 34 years old, compared to 32 years for cases that tested negative. p > 0.05)  .From several anatomical areas, biological samples for STI and HPV genotyping analysis were collected. Mycoplasma spp. (p = 0.035), Staphylococcus aureus (p = 0.009), and MCV (p = 0.022)  .Trichomonas vaginalis , Mycoplasma spp. , Staphylococcus aureus , HSV , and MCV   .p > 0.05) with the chance of receiving a positive STI test.Additionally, we examined the likelihood that having a specific HPV genotype (high or low probability) may increase the likelihood of receiving a positive STI test result. As shown in p = 0.000) and Ureaplasma spp.  (p = 0.048 and p = 0.000). Genotype 6 was a risk factor for MCV . Genotype 66 was a risk factor for HSV 1 and 2 infections   . Genotyp= 0.010) .Treponema pallidum, HSV, Staphylococcus aureus, Klebsiella spp., and Haemophilus spp. In addition, in the second line, we sought the most prevalent pathogens, such as Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma spp.The HPV infection is commonly acquired through sexual contact, and, in most cases, the immune system resolves the infection. However, eventually, the virus remains chronic, a concerning fact due to its association with oncogenic processes and the potential development of lesions or other health issues. Several approaches have been used to deal with the confusing HPV nature, including routine cervical cancer screening and HPV vaccination for advised populations. The current cervical cancer screening guidelines recommend the Papanicolaou test and HPV genotyping , and theIn our study population, we observed that the prevalence of HR-HPV and LR-HPV were similar, 33% and 37.5%, respectively, and the most common HPV genotypes were, in decreasing order, 6, 11, 51, 66, 58, 59, 16, 52, and 39. Although different methods were used to determine HPV genotypes, the results were equivalent to those of earlier studies. The more frequent HPV genotypes included 66, 52, and 51, in addition to 16 ,14,15,16Not all HPV panels typically include LR-HPV genotypes; however, interest in these genotypes has grown due to their potential relevance to carcinogenic processes not only in the cervix but also associated with vaginal intraepithelial neoplasia (VaIN) ,18,19. HUreaplasmas spp. and Mycoplasmas spp. in females, the other common pathogen was MCV, mainly in men. In the case of Ureaplasmas and Mycoplasmas, it is well studied that these microorganisms are acquired from the first instance of sexual intercourse, and during many years, it was believed they were innocuous; nevertheless, those mollicutes are being correlated with poor pregnancy, perinatal outcome, and infertility among men and women [Because the participants of the study were sent exclusively to detect any HPV genotype and there were no other apparent clinical signs or symptoms to suspect having any other infection, the results were surprising. Furthermore, in addition to the high rates of nd women ,23.MCV was the most frequent virus detected in male participants, and there is a lack of evidence for HPV-negative lesions in men where the pathogen present is different, as reported previously . The coeChlamydia trachomatis, Neisseria gonorrhoeae, HSV, and Trichomonas vaginalis were detected. These findings are one of the reasons why we conducted this study, as these pathogens often present subclinically, and patients may continue to develop complications and sexual health outcomes such as infertility and a higher risk of acquiring other infections, such as HPV and HIV. Our results demonstrate the importance of routinely screening patients for these pathogens.One of the main goals of our study was to identify the pathogens present in HPV-positive samples. We found that pathogens such as Trichomonas vaginalis was not a critical pathogen detected in our population compared to other people in Latin America [In our population study, although our data did not show a significant difference, it was noteworthy that HPV-positive samples had a high frequency of positive STI results. Moreover, HPV multiple infections were more frequent in patients with positive results for other STIs. These cellular events are frequently seen by the imbalance of the microenvironment brought on by the dynamic molecular interaction of coexisting bacteria in a particular mucosa, a fact that is commonly thought to be the origin of these cellular processes ,28. For  America ,30. In a America .This project demonstrated that we should prioritize the development of screening tests and apply them intentionally to improve clinical outcomes, prevalence/incidence, and other relevant sanitary information to provide concrete answers for patients. Innovation is necessary to develop new technologies and processes and improve upon and tailor existing ones to different target audiences, environments, or objectives. The most important conclusion is that having solid data on STIs will help targeted programs be more accurate and effective in adopting or adapting services to benefit a more significant number of people, strengthening strategic information systems, and ensuring that data are gathered and used ethically to help communities requiring the cooperation of civil society. Additionally, it will be crucial to establish affordable STI diagnostic tests and more capable laboratories in Mexico and Latin America .Understanding the STI epidemic requires knowing when, how, and among whom new infections are happening. It also entails determining the conditions that facilitate the transmission of STIs or hinder their control and the use of treatments that can help. This information enables prevention programs, treatment, and care to be prioritized and given special attention. Finally, our research findings can influence clinical practice and public health regulations to enhance patient outcomes and stop the spread of STIs.


To enhance the vaccination rate of adolescents against HPV, understanding their current vaccination intentions and identifying the factors that influence their decision to vaccinate are imperative. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to search for relative literature. Five electronic databases  and Korea Citation Index (KCI)) were searched from 2007 to 2022, and 19 studies were selected for final review. The Mixed Methods Assessment Tool (MMAT) was used as a critical appraisal tool to evaluate the quality for various types of research designs. This integrative review revealed three themes, including facilitators , barriers , and ways to increase vaccination uptake (knowledge promotion and HPV vaccines coverage by public insurance). To encourage HPV vaccine uptake, it is essential to enhance public knowledge, create compelling advertisements, and ensure that the vaccines are covered by public insurance. Moreover, providing educational programs that emphasize the effectiveness and significance of HPV vaccines to adults who can influence the vaccination decisions of adolescents is vital. Human papillomavirus (HPV) is the most common sexually transmitted infection in the world, and it is estimated that over 80% of women and 90% of men will be infected with the virus during their lifetime ). HPV haVaccination is an essential tool to prevent and control HPV infection and related complications; the Advisory Committee on Immunization Practices (ACIP) recommends HPV vaccination between the ages of 9 and 26, with a focus on ages between 11 and 12 . The ACIIn order to increase the vaccination of adolescents, it will be essential to understand the current vaccination intention and to identify facilitators and barriers to provide an overview for key stakeholders. The underlying variables that impact individuals’ intentions to vaccinate should be identified, as these intentions act as a precursor to actual vaccination behavior. It is anticipated that individuals would possess the intention to modify behaviors related to health before engaging in indicated behaviors . In manyAt the health provider level, factors that promote vaccination include the provision of vaccination information ,14,15,16Given that vaccination intention is the strongest predictor of HPV vaccination , understSpecifically, this integrative review presents (1) the factors associated with the HPV vaccination among Korean adolescents, (2) the knowledge, intention, vaccination rate of the HPV vaccination among Korean adolescents, and (3) the facilitators and barriers of HPV vaccination among Korean adolescents. Understanding these factors would provide healthcare providers and stakeholders with the essential knowledge necessary to develop strategies that may significantly enhance HPV vaccine uptake among Korean adolescents.The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)  was usedA research librarian helped to find additional articles. Boolean operators and truncation were used with combinations of the keywords in order to identify all relevant articles. The librarians suggested search terms and databases based on the researchers’ study topics. Subsequently, both the researchers and the librarians conducted individual searches. The librarians provided references that the researchers might have missed.The article inclusion criteria were as follows: (1) original studies published in English/Korean language, peer-reviewed journals; (2) studies of participants that were school-aged children aged 8 to 18 in the Korean education system, parents or caregivers of school-aged children and teachers of school-aged children who may influence the vaccination of the student; and (3) papers that identify the purpose of HPV vaccination and the relative factors; knowledge related to HPV vaccination, attitudes toward the HPV vaccination, HPV vaccination behaviors, and HPV vaccination intention. Systematic/literature reviews, opinion pieces, editorials, conference proceedings and studies published in languages other than English and Korean were excluded.A PRISMA flowchart  was usedWe assessed the risk of bias of each study using the MMAT in The data extraction form was rigorously tested using two articles to ensure that the form captured all relevant information. Primary data from all articles were extracted by two researchers (SH and CS), and organized into an Excel table. The extracted data included the author and publication year, methodology, sample, purpose, the findings, and the strengths and limitations. In instances of disagreement, a discussion was conducted with the participation of LJ in order to reach a consensus.Following the completion of the data extraction process, the obtained findings were subjected to analysis and subsequently organized into distinct thematic areas using a thematic analysis approach. We followed Thomas and Harden’s three stages of thematic analysis, namely, coding, organizing codes into descriptive themes, and integrating descriptive themes into analytical themes . In ordeSubjects were varied, including students only (n = 5), mothers (n = 11), parents (n = 1), a mother and daughter pair (n = 1), and teachers (n = 1). The sample size of included studies ranged from 101 to 757. Two studies had a sample size of over 700 participants ,34. ElevFrom the 19 studies, three themes were identified to be related to the factors associated with HPV vaccination among Korean adolescents: facilitators, barriers, and ways to increase vaccination rates.Subthemes for facilitators are personal characteristics and environmental factors. The personal characteristics include attitude ,24,35,36Subthemes for the barriers to HPV vaccination included a lack of awareness and knowledge about HPV, concerns about side effects of the HPV vaccine ,33,34,35A total of 12 out of 19 studies reported the relationship between HPV-related knowledge and HPV vaccination ,37,38,39A total of 11 out of 19 studies were conducted research using a theoretical framework: Health Belief Model  and TheoHowever, there is a limitation because since all of the selected studies were cross-sectional studies it is hard to reveal a causal relationship and changes over time among knowledge, attitude and intention of HPV vaccination. Therefore, it is necessary to conduct longitudinal studies to identify the change of these variables. Through longitudinal studies, changes in intention over time can be observed, and by analyzing these patterns, potential factors for improving vaccination intention can be identified. Additionally, by tracking the vaccination status of individuals who initially had vaccination intentions, insights can be gained into the actual impact of intention on vaccination behavior. Additionally, eighteen studies were descriptive studies, excluding one quasi-experimental study design . QualitaIn addition, there is a limitation in that there was no qualitative study among the selected studies, which might bring a lack of deep understanding of the subject’s experience. There may be a risk of sample bias including recall bias and social desirability bias in that a self-reporting questionnaire was used and convenience sampling was used in limited regional areas in most of the selected studies. For the study subjects, eleven studies were conducted on mothers only, and five studies were conducted on daughters only. In this study, mothers emerged as the primary decision-makers. This is indicative of the Confucian-influenced Korean culture, where mothers traditionally hold a central role as caregivers. However, there is a need to discuss other perspectives that can influence decision-making, such as fathers, relatives, others, and healthcare professionals, reflecting the requirement for a broader discourse. There was only one study conducted on teachers. Therefore, further research includes various subjects that may affect the intention of HPV vaccination in adolescents.The absence of any mention of controlling for potential confounding factors in the studies is a notable limitation. Addressing potential confounders is crucial, particularly when examining vaccination behaviors and beliefs. This could involve adjusting for variables that might influence the relationship between the studied factors and vaccination outcomes, ensuring more accurate and reliable findings. Therefore, it’s important for future research to consider and account for these confounding factors to enhance the validity of the study results. All investigations were exclusively conducted within the confines of the South Korea. It is imperative to underscore that the idiosyncratic cultural, societal, and policy nuances inherent to South Korea may yield findings that are discernibly disparate from research endeavors carried out in alternative nations. Such context-specific intricacies underscore the prudence required when extrapolating these results to dissimilar cultural or policy contexts.Within the framework of a systematic review, the observed significant variance in sample sizes (ranging from 101 to 757) does not pose a substantial concern. This is primarily attributed to the nature of systematic reviews, which prioritize the synthesis and interpretation of existing research findings rather than the execution of fresh statistical analyses. Consequently, there is no substantive basis for apprehension when it comes to the comparison or amalgamation of results across these diverse studies within this review’s purview. Nonetheless, it is advisable to remain open to potential avenues for supplementary analyses in the future, aiming to investigate any latent influence that variations in sample size might exert on the outcomes under scrutiny.This study was conducted to identify factors associated with HPV vaccination among Korean teenagers through an integrative review and to provide basic data for education and promotion programs that might increase vaccination rates among Korean teenagers. We reviewed 19 articles to investigate the facilitators and barriers to HPV vaccination among Korean teenagers. Three themes emerged from this integrative review: facilitators of HPV vaccination, barriers to vaccination, and ways to increase vaccination uptake. The facilitators of HPV vaccination uptake include personal characteristics and environmental factors. Individual factors were knowledge about vaccination and self-efficacy and environmental factors were described as family history of cervical cancer, clinician’s recommendation, and mother or teacher’s awareness of the importance of HPV vaccination. The barriers include a lack of awareness and knowledge about HPV of parents including both fathers and mothers, or clinicians, concerns of the side-effects of the vaccination, and the burden of costs. We also provided ways to increase vaccination uptake based on the findings from the integrative literature review. We created a diagram to show the themes as shown in While the majority of the studies examined in the review emphasized the significance of experience and awareness, it is important to note that the correlation between vaccine-related knowledge and intention to vaccinate remains complex. Despite this weak correlation, possessing sufficient knowledge related to vaccines serves as a reinforcing factor, compared to a lack of knowledge and awareness that becomes a hindrance. Korean adolescents have less knowledge about the HPV than their Western counterparts . The knoThere may be gender differences in HPV vaccination between male and female students. In general, the HPV vaccine vaccination and completion rates for male are lower than for female ,47. TheyThe fear of side effects becomes a barrier to vaccination rate, as stated in five articles ,37,38,39People around adolescents such as mother, family, teacher, and health professionals are likely to influence the HPV vaccination rate. The mother’s experience with HPV vaccination was a significant predictor of their children’s’ HPV vaccination status. For the mothers of sons, subjective norms, attitudes, and perceived behavioral control were found to be significant predictors of intention to obtain HPV vaccination . A familHowever, mothers of elementary school girls often have inaccurate information about the appropriate age for their children’s HPV vaccination . Some paAt the community level, schools are central in accommodating education about HPV including HPV vaccination and screening  through Besides family and school, healthcare providers play an important role in educating adolescents and their parents. Girls were more willing to receive the HPV vaccination if it was recommended by clinicians or parents than by friends or teachers ,30,32,39In this review, health care provider recommendation was identified as a reinforcing factor associated with HPV vaccination. This is consistent with research in several other countries , which sWhen a healthcare provider has a higher level of knowledge, they are more likely to recommend vaccines to their patients . ConversA further predictor of their daughter’s HPV vaccination was the mother’s health beliefs. The most often occurring predictors were perceived benefits and perceived barriers. In the reviewed papers in this study, the high cost of vaccines is one of the alleged barriers. The vaccination is necessary to receive three times to get the effect but each cost is about KRW 200,000 which is equal to USD 180 and total of three shots is about KRW 600,000 (=USD 540).A policy is needed to expand the number of free vaccinations  from womHPV vaccine requires a second or third dose depending on age. This means it is important not only to start getting the vaccine but also to complete the second or third dose. Vaccine completeness is known to be significantly lower than the rate of getting first doses , and vacIn Korea, there is a study showing that preventive education based on Planned Behavior theory is applicable to college students  and a stSince this review included only published papers, studies with less impressive results may have been excluded. Additionally, the search terms and methods used to finally select papers may have resulted in missing some papers, which may bias our findings and assumptions. Since this study was conducted considering only Korean populations, there are limitations in generalizing the results of this study to HPV-related research, but it may have the advantage of comparing various barriers and facilitators between countries.The three themes of this review’s findings imply the need for nurses to accommodate all of these aspects to increase HPV vaccination in both male and female adolescents. Approaches can be made for individuals, families, communities, health professionals, and policymakers.Individual and family approaches will be very closely related because HPV vaccination in adolescents is likely to be influenced by the knowledge and experience of the mother, as well as the experiences of family members about cervical cancer. Health education can be carried out through various teaching methods and media, and use developmentally appropriate interventions including interactive discussions, informative presentations, role-playing scenarios, informative videos, quizzes, and interactive simulations. When clinicians or educators conduct health education, it is necessary to pay attention to the psychological condition of parents because it involves family values such as the belief that HPV vaccination is related to sexual activity in adolescents. To counteract such misconceptions, public health campaigns aimed at correcting misinformation is crucial.Involvement of the community such as school teachers cannot be ruled out as their experience with the pap test and awareness increase the possibility of vaccination in adolescents. Therefore, nurses could assess teachers’ knowledge and experience to better equip them to have a positive influence on parents’ and adolescents’ decision-making regarding HPV vaccination. It is also important to encourage schools to participate in the promotion of HPV vaccination by incorporating information about cancer and HPV vaccination into the curriculum and by becoming HPV vaccination sites through school nurses. This adjustment could also involve integrating comprehensive sexual health modules into the curriculum that provide students with information about the significance of HPV virus and HPV vaccination. By doing so, students can become informed about safeguarding their health and making informed decisions regarding preventive measures. Additionally, workshops and interactive sessions could be organized to address questions, concerns, and misconceptions surrounding HPV vaccination, fostering an environment of open dialogue and knowledge dissemination. This approach would empower students with the necessary information and encourage proactive engagement with their sexual health and well-being.Health professionals have a crucial role in imparting health education to individuals, families, and communities. They provide essential information and guidance on various aspects of well-being, such as disease prevention, healthy lifestyles, proper nutrition, and fitness. This empowers people to make informed decisions about their health. Health professionals should first be provided with sufficient information about HPV vaccination and techniques to approach adolescents, families, and communities when educating them. This improves their ability to understand the reasons why some adolescents remain unvaccinated and determine appropriate education methods for adolescents and families.As an example of this role, health professionals can employ tailored reminder messages and digital platforms to enhance vaccination adherence. Tailored reminder messages can play a pivotal role in prompting individuals to adhere to their vaccination schedules. However, discussing the broader aspects of follow-up, such as establishing structured communication channels between healthcare providers and vaccine recipients, as well as leveraging digital platforms for appointment scheduling and tracking, would underscore the importance of seamless vaccination continuity.Recognizing potential limitations and challenges in implementing these interventions strengthens their essential role in comprehensive vaccination strategy. These could include factors like vaccine hesitancy, accessibility to healthcare facilities, and cultural barriers. Addressing these challenges might involve community engagement efforts to dispel misinformation, mobile vaccination clinics to reach underserved populations, and culturally sensitive educational materials. Acknowledging both the benefits and potential difficulties can provide a more balanced assessment of the proposed interventions’ feasibility and impact.Nurses can also advocate for policy changes regarding free vaccination expansion of the age and gender coverage through greater insurance coverage for HPV vaccination for female and male adolescents. An analysis of the cost-effectiveness of HPV vaccination can be carried out by comparing the costs of vaccination interventions and future cases of HPV to show a compelling reason to increase insurance coverage. Nurses are central to advocating for policies that could potentially boost the HPV vaccination uptake.Furthermore, we suggest the need for specific and actionable interventions to enhance HPV vaccination rates through efforts that go beyond knowledge and awareness, incorporating a more behavioral dimension. This includes implementing educational workshops, online modules, or community outreach programs. The growing influence of digital media in health education is not adequately addressed. Mobile apps, text reminders, or interactive online platforms could be considered as tools for education and reminders. Furthermore, it is essential to collaborate with the media to dispel misconceptions about the HPV vaccine and promote the importance of vaccination.In addition, it is necessary to consider how the success of the proposed interventions will be measured. For example, it should explore not only an increase in vaccination rates but also intermediate metrics like increased awareness, positive attitudes towards vaccination, and improvements in adolescent sexual health knowledge. Given the sensitive nature of topics like sexual health in certain cultures, these strategies could benefit from further emphasizing the importance of culturally sensitive approaches. In addition to the broader cost-effectiveness analysis of HPV vaccination, the review could suggest smaller economic incentives, such as discounts or vouchers, to encourage vaccination.Preventive HPV vaccination in adolescent boys and girls has the potential to significantly reduce a variety of HPV-related morbidity and mortality. This study was conducted to identify the factors that influence female and male HPV vaccination intention considering personal, parental psychosocial, and environmental factors. After reviewing the studies, barriers and facilitators were identified. The findings highlight the importance of an approach that considers individual, family, community, and policymaker aspects to increase HPV vaccination coverage.In order to increase the vaccination uptake, various techniques, such as educational events and curriculum adjustments, should be implemented. Moreover, because clinicians’ recommendations are a facilitator of parents’ decisions to vaccinate their children, involving both male and female adolescents, parents, as well as clinicians in school-based immunization programs or educational events may contribute to increasing vaccine immunization rates. Since economic issues are a major consideration for HPV vaccination, further expansion of vaccination cost support for economically vulnerable groups should be included, and customized notification messages and educational interventions to complete the entire vaccination process will be recommended.The studies analyzed for the review did not include qualitative research, the study subjects were mostly female adolescents, and there was a lack of research targeting medical providers. Future research to promote HPV vaccination will require an in-depth understanding of the subjects through qualitative research. Additionally, a review of papers targeting only male adolescents would be meaningful, and it is necessary to conduct research on medical staff to deepen our understanding of them.