Via multivariate analyses, only positive endocervical instead of ectocervical margins ; p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 ;  Human papillomavirus (HPV) is one of the most common sexually transmitted diseases worldwide . HPV is The different HPV types are classified into “oncogenic” and “non-oncogenic”, according to the capacity to integrate their own genetic material into the DNA of the host cells . The IntRisk factors related to the transmission of the virus are mostly related to sexual habits: unprotected sexual practices, multiple partners and the onset of sexual activity at an early age. However, failure to vaccinate before the onset of sexual activity, immunosuppression and exposure to other sexually transmitted diseases also increase the possibility of contracting the infection and developing cervical lesions. In the male, the development of precancerous lesions is an ascending problem, particularly among populations exposed to a higher risk of contracting the infection .Most HPV infections regress spontaneously without sequalae , but in The risk of recurrence after surgical treatment for CIN 2-3 is not negligible, ranging between 5 and 10% at 5 years ,14. SeveWe performed a multicenter retrospective study. Data of consecutive patients with newly diagnosed high-grade cervical dysplasia (HSIL/CIN2/CIN3), treated in Italy between 1 January 2010 and 31 December 2014, were collected into a dedicated database. The Institutional Review Board was obtained.Inclusion criteria were: (i) histologically confirmed diagnosis of high-grade cervical dysplasia (CIN 2-3); (ii) the execution of cervical conization; (iii) description of margins status, both endocervical and ectocervical, at histology; (iv) persistence of the HPV infection detected during a pap smear performed 6 months after the surgical treatment; and (v) 5-year follow-up .Patients excluded from the study were: (i) patients under the age of 18 years, (ii) those who had not provided informed consent for participation, (iii) those undergoing therapeutic procedures other than those analyzed in the present study, (iv) those suffering from invasive carcinoma at the time of conization, (v) those suffering from glandular lesions, (vi) those with an ongoing pregnancy and (vii) those who had had a previous total hysterectomy.The primary endpoint of the study was to assess the outcomes of patients considered at high risk of recurrence (those with positive margins and persistent HPV infection). As secondary outcomes, we tried to identify predictive factors that might influence the risk of developing persistence and recurrence in this high-risk patients’ group.Data collected included patients’ demographics, baseline characteristics, viral genotype, surgical treatment mode and status of surgical resection margins, persistence of HPV infection after conization (at 6 and 12 months), vaccination status as well as follow-up after surgery. Although patients were treated in different centers and by different surgeons, there were no differences in terms of patient care and services’ facilities over the study period.®), Cobas®, Clart® [Data were collected into dedicated databases updated on a regular basis by residents and trained nurses. All patients included underwent conization with direct colposcopic guidance. All patients underwent an outpatient follow-up at 6 and 12 months after surgery. Follow-up included: medical examination, outpatient colposcopic evaluation and p ap smear. Methods used for the detection of HR-HPV before and after treatment differed between centers . No sigBasic descriptive statistics were used to describe the study population. The risk of developing recurrence was evaluated using Kaplan-Meir and Cox proportional hazard regression models. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated for each comparison. Univariate and multivariate analyses were performed when appropriate. Statistical analyses were performed using GraphPad Prism version 6.0 , IBM-Microsoft SPSS  version 20.02 . Among the 163 patients, 102 (63%) and 73 (44.7%) had a diagnosis of CIN 3 and were HPV 16/18 positive, respectively. Twenty-five patients (15.3%) underwent HPV vaccination after primary treatment. Among the 2833 patients not included in the analysis, only 67 (2.36%) underwent adjuvant vaccination for HPV. Indeed, no impact on recurrence has been detected in this group as well.Overall, 2966 patients underwent conization for CIN2-3 during the study period. All patients were screened to identify HPV genotype(s) before conization. Positive ectocervical and endocervical margins were observed in 119 (73%) and 44 (27%) women, respectively. No patient had both margins positive. We evaluated risk factors for developing recurrence after conization over the 5-year follow-up period. n = 61) and CIN3 (n = 102). The prevalence of endocervical margins was higher in the CIN3 instead of the CIN2 group. p = 0.035) and positive endocervical instead of ectocervical margins ; p < 0.001) are associated with an increased risk of persistence/recurrence ; currence .p = 0.021) were associated with worse outcomes ; outcomes .The present paper evaluated the outcomes of patients at high risk of recurrence following primary treatment of cervical intraepithelial neoplasia. High-risk patients are considered patients with positive cervical margins and HR-HPV infection persistence. This study is the first to our knowledge to assess the contextual presence of positive margins after surgical treatment and HPV persistence. It reports interesting findings. First, among women treated with primary conization, the high-risk population  accounts for about 5%. Second, positive margins after treatment, both ecto- and endocervical, were more frequent in patients with CIN 3 than in patients with CIN 2 at final histology. Third, also among women with persistent HR-HPV infection, patients with positive endocervical lesions have a higher recurrence rate than patients with ectocervical lesions. Fourth, the use of HPV vaccination did not improve the outcomes of the high-risk group.Recurrent cervical dysplasia might cause severe issues to women’s health, and it is associated with a significant risk of cervical cancer, and in women willing to preserve their childbearing potential, the execution of multiple conizations might affect fertility and reproductive outcomes. For this reason, surveillance of these patients is delicate, and HPV testing and co-testing, showing little difference in detecting recurrent CIN2+, could be used. Persistence of HR-HPV infection, especially HPV 16/18, are considered independent predisposing factors for recurrence/progression of CIN2+ and cervical cancer. Accumulating evidence suggests that positive cervical margins and HPV persistence are the main risk factors impacting the risk of recurrence ,22,23. Rvs 56%) and equivalent specificity (84%) [A growing body of the literature reported data reflecting positive margins. Complete excision of cervical lesions is the main goal to be achieved in surgical treatment, but full excision rates are about 85–90% ,25. Yungty (84%) . For thiA recent retrospective cohort study of 2400 women diagnosed with CIN2+ identified individual risk factors that increase HSIL recurrence rates: endocervical canal length, compromised margins and HIV+; an excised canal length of 1.25 cm or more seems to reduce the recurrence rate . Few stuSome points of the present study that should be considered: (i) Our analysis showed that there is no difference in risk of persistence/recurrence for infection with HPV16/18 and other HR-HPV. Although accumulating data support that those with HPV16/18 are at a high risk of persistence in comparison with other HPV types , no studAnother key concept for reducing the number of precancerous and cancerous lesions associated with HPV infection is the spread of the vaccine among male individuals, especially during adolescence.Unfortunately, as demonstrated in a recent systematic review and meta-analysis conducted by Amantea et al., in which the data from eight studies on more than 140 thousand men aged between 18 and 30 years have been analyzed, the adherence to vaccination is about 11%, with a percentage of adhesion inversely proportional to the increase in age .In Italy, a group of researchers commented on the recommended vaccine for the prevention of infection with HPV in men, designating the vaccine as the preferred treatment . HoweverHowever, cross-protective efficacy is controversial, as a 2012 meta-analysis showed that the use of a bivalent vaccine protected against some non-vaccine HPV types .The main weaknesses of the present paper included its retrospective nature and the consequent biases related to its design. Data about specific virus types and possible multiple types of infection were not available. The strengths of our work include the large sample analyzed, the multicenter design and the homogeneity of the patients included. It would be interesting to analyze the comorbidities of these patients in relation to disease progression and long-term obstetrical outcomes. In conclusion, this manuscript analyzes the data of a large sample of patients undergoing conization for cervical dysplasia. In this population, positive endocervical margins after surgical treatment are related to a statistically significant increase in the persistence/recurrence rate. During follow up, the correlation between cervical lesions and HR-HPV genotypes has a fundamental role: high-risk HPV has the highest accuracy in predicting recurrence. Given the higher risk of recurrence with positive margins, wider excisions could be indicated to avoid residual lesions. Timely identification of these high-risk patients enables risk stratification and enables individualized management and follow-up strategies. Further prospective studies are necessary to assess the most appropriate follow-up strategy in women with cervical dysplasia and to better understand the role of vaccination in these risk categories.


Human papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center.A total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed.In both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%).High grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China. Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death among women globally, especially in developing countries. It has been estimated that there were about 604,000 new cases and 342,000 deaths worldwide in 2020 . In ChinTherefore, this study analyzed the peak age of HSIL and the correlation between different HPV genotypes and HSIL, in order to provide clinicians with evidence-based medical data on the significance of peak age and different HPV genotypes in cervical opportunistic screening.We collected the cervical cell samples of women who visited the gynecological clinic of our hospital and accepted HPV genotyping test between October 2017 and May 2020. Inclusion criteria: (1) HPV16/18 positive or positive cytology  with HPV other types positive or negative cytology but persistently positive for HPV other types (more than 1 year). (2) had biopsy-confirmed histology results within 6 months after HPV genotyping test. Exclusion criteria: (1) previous history of cervical lesions; (2) previous history of cervical surgery; (3) histology results were followed up for more than 6 months. The standard of colposcopy referral followed the 2012 ASCCP guideline and the expert consensus on colposcopy application in China [Individual cervical samples were collected by gynecologists using a swab and placed in the preservative kit provided by the manufacturer of the HPV kit.The HPV genotyping test was based on polymerase chain reaction (PCR) and TaqMan technology, using the commercially available HPV Genotyping Real Time PCR kit , which could simultaneously detect 17 HPV types  [Immediate histological correlation results including cervical biopsy, endocervical curettage, or loop electrosurgical excision procedure/cone biopsy performed within 6 months of HPV genotyping tests were included in this study. The histopathologic diagnoses were rendered by 2 experienced pathologists in our hospital. Histology results were categorized into negative , CIN1, CIN2, CIN3 and SCC according to the 4th edition of WHO classification of the female genital tumors . CIN2+, P value was used to indicate the significance, the test level was α = 0.05, and P < 0.05 was considered statistically significant.SPSS v25.0 was used for statistical analysis. The count data were expressed as a percentage or n (%). The prevalence of HPV across cervical lesions was compared by Chi-square test. The 2 = 14.577, P = 0.006). As the results showed in Fig. 2 = 5.906, P = 0.052), respectively. However, the results for multiple HPV infection were contrary to the results for single infection and CIN grade association. The overall percentage of multiple HPV infection was 38.77% (592/1661). As shown in Fig. 2 = 5.906, P = 0.052).A total of 24,199 samples with HPV genotyping results were collected, the overall positive rate of HPV was 23.10%. Among the 24,199 samples, 1,661 cases with histopathologic diagnoses were included in this retrospective study. 456 women were diagnosed as negative by pathology, 1,199 women were CIN, and 6 women were cervical cancer. Among the women diagnosed with CIN, 899 (75.29%) were CIN1, 156 (13.06%) were CIN2, and 144 (11.65%) were CIN3. HPV-positive results reported for negative, CIN1, CIN2, CIN3 and SCC were 91.45%, 90.99%, 98.08%, 96.53% and 100%, respectively (χP < 0.001).In this study, the evaluation values of women infected with single HPV16 type in pathologically normal CIN1, CIN2, and CIN3 were 24.07%, 22.06%, 46.24%, and 55.21%, respectively. The proportion of women infected with monotype HPV16 increased significantly with the increase of CIN grade . In addition, among women with pathological normal, CIN1, CIN2 and CIN3, the incidence of HPV16/18 (HPV16 and/or HPV18) was 33.33%, 29.41%, 50.54% and 59.38% respectively . However, the prevalence of HPV51, 56 and 66 were lower than 8.00% in all the pathological CIN grades and decreased obviously with the increasing grade of CIN . Then, in normal pathology, CIN1, CIN2, and CIN3, the incidence of other high-risk human papillomavirus (hrHPV) types (excluding 16 and 18) was 5.93%, 69.54%, 49.46%, and 40.63%, respectively. In conclusion, with the increase of CIN grade, the percentage of non-HPV16/18 of hrHPV also showed the same downward trend .It is also observed that HPV33 and HPV16 have the same trend, that is, HPV33 infection rate increases with the increase of CIN grade. The prevalence of HPV33 in normal, CIN1, CIN2 and CIN3 were 2.22%, 3.15%, 5.38% and 8.33%, respectively  was 67.41%. In CIN1 patients, the 5 most common HPV types were HPV16 (22.06%), HPV52 (17.02%), HPV58 (14.92%), HPV18 (7.35%) and HPV66 (7.14%), with a total incidence of 68.49%. The total incidence rate of five major hrHPV genotypes in CIN2 women was 89.25%, which was HPV16 (46.24%), HPV52 (15.05%), HPV58 (15.0%), HPV31 (7.53%), and HPV33 (5.38%), respectively. In the CIN3 group, the infection rate of the first five hrHPV genotypes accounted for 88.54%, and the prevalence rate was HPV16 (55.21%), HPV58 (11.46%), HPV52 (9.38%), HPV33 (8.33%), HPV31/18 (4.17%), respectively. Moreover, no monotypic infection of HPV45 and HPV6/11 was observed in CIN2 and CIN3 in this study. In addition, all of the six SCC cases were detected with single HPV16 genotype results. (Shown in Table .P < 0.001). Even though the prevalence of HPV33 in all CIN grades was lower than 10%, HPV33 also increased with the increase of CIN grade . However, HPV18, 31, 52, 58 showed the opposite trends, which decreased with increasing grade of CIN. Besides, other HPV types also decreased with increasing grade of CIN . Regarding single infection, the cumulative positive rate of HPV16, 18, 31, 33, 52 and 58 was 68.15%, 66.60%, 93.55% and 92.71% in pathologic normal group, CIN1, CIN2 and CIN3, respectively.As shown in Fig. To detect one CIN2 + cases, 2.8, 8.5, 3.2 and 7.1 women should receive colposcopy referrals if using HPV16, HPV18, HPV16/18 and non-HPV16/18, HPV others as screening methods for detecting cervical lesions, respectively. Meanwhile, to detect one CIN3 case, the referral numbers for HPV16, HPV18, HPV16/18, and HPV others were 5.0, 17.0, 5.9 and 15.4 women, respectively. The colposcopy referral rate for HPV others is 2.5 times and 3 times higher than HPV16 for detecting one CIN2 + case and one CIN3 case, respectively  years and (40.75 ± 10.51) years, respectively. In CIN2, the main age was 35 ~ 44 years (36.46%) and 25 ~ 34 years (33.33%), and the prevalence of CIN2 decreased obviously with increasing age in women over 45 years old. While the peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%), and decreased obviously with increasing age. Moreover, no single type infection was identified under 25 years old in both CIN2 and CIN3 (Fig. When age-dependent prevalence for single-type HPV infection in negative, CIN1, CIN2 and CIN3 were evaluated, the top 5 most frequent HPV types in different age groups were analyzed and showed in Fig. In the present study, the overall HPV-positive rate of the opportunistic screening was 23.10%, and the HPV-positive rate reported in the negative pathology, CIN1, CIN2, and CIN3, were 91.45%, 90.99%, 98.08% and 96.53%, which were higher than the positive rate in cervical cancer screening . In addiWhen evaluating cases with single-type HPV infection, HPV16 and 33 increased significantly with the increase of CIN grade, while HPV18, 31, 52 and 58 showed the opposite trend. Besides, all of the six SCC cases in this study were infected with single-type HPV16. These results show that HPV16 was the most aggressive hrHPV in the development of cervical precancerous lesions and malignant cancer. Compared with other HPV genotypes, HPV16-infected cervical lesions were less likely to regress, which was consistent with previous studies . MoreoveHPV genotype distribution in high-grade cervical lesions has been reported to vary significantly in different geographic population , 28. AccIn the present study, the incidence of high-grade cervical lesions was significantly higher among women age 25 ~ 34 years and 35 ~ 44 years than among the other age groups, the results were slightly different from previous studies. In the previous population-based study in Beijing, the peak age of CIN2 + was 30 ~ 34 years . BesidesIn summary, age-dependent distribution suggested that high grade CIN peaks at 25 ~ 44 years of age, women aged 25 years and older in China are recommended for a routine screening if conditions permit. For women ≥ 65 years old, infection with other HPV types should also be taken seriously. For women at 25 to 64 years old, HPV16 was particularly aggressive in the development of cervical premalignant lesions and malignant lesions. In the single-center data, HPV16-positive patients should be given high priority in opportunistic screening because almost one in three HPV16-positive patients would likely to be diagnosed with CIN2/3 in the opportunistic screening, while HPV45 suggested low risk of CIN2/3 in the single-center study. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in high grade CIN, vaccines including these main genotypes might be of great value for cervical cancer prevention in China. The current study was a single-center and retrospective analysis with a relatively small sample size, further confirmation and validation are needed in future multi-center prospective studies with large samples to provide data for opportunistic screening.


Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037).  The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access. Papillomaviridae family and contains non-enveloped particles and double-stranded DNA genomesHuman papillomavirus (HPV) belongs to the Women living with HIV (WLWH) have a higher frequency of multiple infections, anogenital warts, intraepithelial lesions, and anogenital cancers resulting from HPV infectionHPV surveillance in WLWH is important because cervical cancer is considered an opportunistic disease in this group, as these women are more likely to develop preinvasive lesions that, if left untreated, can rapidly progress to invasive cancerCytology has been the primary screening tool for cervical cancer since its introduction into the Brazilian screening program in the 1970sWe conducted a cross-sectional study of WLWH aged 18-64 years who had already had sexual intercourse across all five geographic regions of Brazil, from May 2021 to May 2022. The sample size was calculated by estimating that the proportion of women who underwent molecular HPV testing but did not undergo an up-to-date Papanicolaou (Pap) test would be 50%, requiring a sample size of 278 women per study site. Eight reference services for HIV/AIDS were included in the following cities: Pelotas and Florianópolis (southern region); São Paulo, Vitória, and Juiz de Fora (southeastern region); Brasília (midwestern region); Salvador (northeastern region); and Manaus (northern region). All WLWH aged between 18 and 64 years attended these services, and those who had already started sexual activity were invited to participate. The exclusion criteria were pregnancy, previous hysterectomy, and gynecological cancer. The study was approved by the Research Ethics Committees of the following participating centers: Universidade Federal de Pelotas (UFPel) Medical School, approval number 4,567,941 (CAAE: 43223521.7.1001.5317); STD/AIDS Reference and Training Center, approval number 4,692,020 (CAAE: 3223521.7.2002.5375); Cassiano Antônio de Moraes University Hospital affiliated with Universidade Federal do Espírito Santo (HUCAM/UFES), approval number 4,685,258 (CAAE: 43223521.7.2004.5071); Universidade Federal de Santa Catarina (UFSC), approval number 4,704,088 (CAAE: 43223521.7.2001.0121); Juiz de Fora School of Medical and Health Sciences, approval number 4,718,416 (CAAE: 43223521.7.2009.5103); “Doutor Heitor Vieira Dourado” Tropical Medicine Foundation, approval number 4,768,641 (CAAE: 43223521.7.2005.0005); Bahia State Department of Health (SESAB), approval number 4,829,852 (CAAE: 43223521.7.2003.0052); and Health Science Teaching and Research Foundation (FEPECS/SES/DF), approval number 5,000,655 (CAAE: 43223521.7.2006.5553). While attending the healthcare facilities, eligible women were informed of the study objectives and invited to participate. Those who agreed to participate provided written informed consent.All women who agreed to participate answered an interview in which they provided sociodemographic and behavioral data , received information on the method of self-collection of vaginal samples, and were asked about their health status. The women were also instructed on how to self-sample for molecular HPV testing according to the manufacturer’s instructions. Each study participant received a self-sampling kit and an information leaflet, which was read together with a trained health professional, who also answered any questions the participant might have had about the procedure. The participants individually self-collected vaginal samples in a private bathroom or room, without supervision, and delivered their samples to a health professional. Health professionals identified the samples by applying a pre-established coding scheme (anonymous codes). If any of the women had intercourse, vaginal cream, vaginal medication, or a vaginal or anal intimate shower in the last 48 h, it was registered. All samples were stored in accordance with the manufacturer’s instructions until they were sent to the laboratory for molecular HPV testing. DNA was extracted from all samples using the ReliaPrep™ Blood gDNA Miniprep System  according to the manufacturer’s instructions. The Anyplex™ II HPV28 detection assay  was used for the qualitative detection of HPV DNA, discriminating the results into the following genotypes: 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, 82, 6, 11, 40, 42, 43, 44, 54, 61, and 70. Dual priming oligonucleotide (DPO)-based real-time polymerase chain reaction (PCR)  detects all 28 HPV genotypes using the tagging oligonucleotide cleavage and extension (TOCE) technology with melting curve analysis . This technology allows detection of multiple targets in a single real-time PCR fluorescence channel. According to the manufacturer’s instructions, 5 μL of DNA was added to each of the two wells containing 15 μL of reaction mixture (primer sets A and B). Real-time PCR amplification was performed in a CFX96 thermocycler , and HPV L1 and human beta-globin genes were used as internal controls to monitor the efficiency of DNA purification and PCR inhibition. The test results were sent to the primary care provider at each site for follow-up. In the case of HPV-positive results, a follow-up visit with a clinician was scheduled for guidance and treatment according to the guidelines of the Brazilian Association for the Lower Genital Tract Pathology and ColposcopyStatistical analyses included the overall prevalence of HPV, low-risk HPV, probable high-risk HPV, high-risk HPV, and high-risk and/or probable high-risk HPV infections in the study population. HPV types were classified: low-risk , probable high-risk , and high-risk . Additionally, factors associated with HPV infection have been described, such as socioeconomic status, age, race/skin color, age at onset of sexual activity, and lifetime number of sex partners. The statistical analyses were performed using STATA, version 16.1 (StataCorp). Comparisons between women included in the study and those who refused to participate in terms of skin color and age were tested formally using the chi-square test in the case of proportions of skin color and the t-test to compare means of age. The following independent variables were analyzed: age, in complete years, categorized into four groups ; education level, in years of schooling, categorized into four groups ; self-reported race/skin color, collected according to the five categories of the Brazilian Institute of Geography and Statistics -due to the small number of women who self-reported as yellow (Asian descent) and red (native Brazilian), these two categories were not considered in bivariate analyses; marital status, collected and analyzed into four groups ; age at first sexual intercourse, categorized into four groups ; lifetime number of sex partners, categorized into four groups ; and parity, categorized into four groups . Exchange of sex for drugs or money over the past 12 months was used as a dichotomous variable. Smoking status was divided into three categories: never smoked, former smoker, and current smoker. Data on alcohol consumption in the previous month were classified into four categories: never, less than once a week, at least once a week, and every day.Three primary outcomes were assessed: (a) infection with high-risk HPV, (b) infection with probable high-risk HPV, and (c) infection with high-risk HPV and/or probable high-risk HPV. For each outcome, the denominator was the total number of tests with valid results  and the numerator was the presence of at least one HPV type in each category . Poisson regression with robust variance was used for the adjusted analysis of factors associated with HPV infection in WLWHOf the eight healthcare facilities included in the study, 2,069 WLWH were invited to participate, 1,919 of whom agreed (92.8%) and 150 refused (7.2%) to participate. The women who refused to participate had a median age of 46.9 years (mean 45.5 years); 45.0% self-reported as White, 27.5% as Brown (mixed-race), and 27.5% as Black. Refusals were more common among white and brown women than among black women (p < 0.01); however, there was no difference in terms of mean age (p = 0.4). The number of self-collected vaginal samples per site ranged from 86 (Florianópolis) to 295 (Manaus) with a mean of 240 samples per site. The total number of vaginal samples self-collected by WLWH was 1,919, but five samples (0.3%) were considered invalid by the laboratory, for a total of 1,914 samples (99.7%) analyzed for detection of HPV DNA. The median age of the 1,914 WLWH participating in the study was 45 years (mean 44.7 years). Regarding race/skin color, 31.1% self-reported being white, 42.5% as brown (mixed-race), 24.6% as black, and 1.8% as yellow (Asian descent) or red (native Brazilian). Most participants were ≥ 40 years (68.8%), had 9 to 11 years of schooling (41.4%), and self-reported living with their husbands or partners (47.1%). More than half of the participants (57.5%) were 15 to 18 years of age at their first sexual intercourse and had one or two children (56.6%); 51.7% had had more than four sex partners throughout life. Only 14 participants (0.7%) reported exchanging sex for drugs, and 32 (1.7%) for money in the past 12 months . Out of the 1,914 women living with HIV who were interviewed, 579 (30.2%) had no information on vaccination status, and only 9.9% reported having been immunized against HPV. Taking into account STI infections in the past 12 months, 7.6% (n = 146) of the participants reported being diagnosed with an STI by a physician. Additionally, 26 (1.4%) women indicated that they were unsure whether they had ever been diagnosed with an STI. The most frequently reported STIs were syphilis, herpes, and genital warts.Of 1,914 WLWH who had valid test results, 49.6% had high-risk HPV , 16.7% had probable high-risk HPV , and 40.0% had low-risk HPV (95% CI: 37.8-42.2). The prevalence of high-risk and/or probable high-risk HPV was 53.8% (95% CI: 51.6-56.0), whereas the prevalence of any HPV type  was 65.8% (95% CI: 63.7-67.9).At least one high-risk HPV or probable high-risk HPV type was detected in the samples of the 1,269 women who tested positive for HPV (66.13% [95% CI: 64.0-68.2]). Of these, 74.8% (95% CI: 72.3-77.1) had at least one high-risk HPV type and 25% (95% CI: 22.9-27.7) had at least one probable high-risk HPV type. The factors associated with probable high-risk and/or high-risk HPV infection in the univariate analyses were age, education level, lifetime number of sexual partners, exchange of sex for money (past 12 months), and alcohol consumption (last month) . Regardi2 = 96.98%; p < 0.001), with a prevalence of high-risk HPV of 40% , of which the most reported types were HPV-16 (16%) and HPV-58 (6%)The HPV prevalence found in WLWH in the eight HIV specialty healthcare facilities distributed across eight Brazilian states was 49.6% for high-risk HPV and 16.7% for probable high-risk HPV. This prevalence was higher than that of a multicenter study conducted in Brazil, which reported a 28.4% prevalence of high-risk HPV in WLWH,In the present study, in which most participants were ≥ 40 years, more than half reported having their first sexual intercourse between 15 and 18 years of age, and a higher prevalence of high-risk HPV was observed in women aged 18-29 years. We observed an inverse association between the presence of high-risk HPV (p = 0.003) and low education levels, which is consistent with the findings of Monteiro et al. (2021)A limitation of this study is that some interview questions addressed intimate matters that relied on the recall of past events, which may have underestimated the risk factors for certain morbidities associated with sexual and reproductive health. However, the high participation rate and few lost samples highlight the importance of this study, with representation across all five geographic regions of the country, to produce evidence for the development of public policies for WLWH in Brazil. The large number of unanswered responses to the vaccination question made it impossible to analyze the presence of HPV infection and vaccination status. Information on CD4 count, viral load, and antiretroviral treatment was not collected. The questionnaire was summarized to reduce the interview and collection time for the WLWH, as we took advantage of any type of contact the woman had with the service. There is a growing awareness of the need to maximize synergies between the HIV/AIDS response and efforts to prevent, diagnose, and treat cervical cancer through HPV vaccination, education, screening, and treatment strategies. Similarly, existing HIV programs can play a strategic role in expanding cervical cancer prevention services-,,,Several health systems have considered switching from cytology to HPV DNA testing for cervical cancer screening based on randomized trials that have demonstrated the superior effectiveness of the latter, with improved sensitivity for detecting lesions, that is, reducing the risk of false-negative results, and extended screening intervals when HPV is not detectedThis study used a self-sampling strategy to optimize the primary screening of WLWH during routine visits to an infectious disease service. Self-collection of vaginal samples for HPV testing has high sensitivity for detecting precancerous and cancerous lesions, with an accuracy similar to that of clinician-collected samples


This descriptive retrospective cohort analysis included 6056 women who presented to our facility between June 2016 and March 2022 for cervical precancer screening via HPV testing. A large majority of this cohort underwent AmpFire testing (55.8%), followed by careHPV (23.3%), MA-6000 (14.7%), and GeneXpert (6.1%). MA-6000 showed the highest hr-HPV positivity rate of 26.4% , followed by AmpFire . GeneXpert and careHPV showed similar hr-HPV positivity rates of 14.8%  and 14.8% , respectively. For the AmpFire and MA-6000 platforms, which utilize similar detection and reporting formats, we found a significant excess detection rate of 9.2%  for MA-6000 compared to AmpFire. At the genotype level, MA-6000 also detected significantly higher rates of HPV 16 and other hr-HPV types  than AmpFire; there was no difference in detection for HPV 18. Based on our experiences and preliminary analysis, we believe that the choice of HPV testing platform cannot be accomplished with a one-size-fits-all approach. Factors worth considering are the financial implications of platform acquisition, costs to clients, and throughput when screening programs are not sufficiently large. We describe our successes and challenges with the different platforms which we believe will be helpful to centers in low-income countries as they transition into using HPV DNA testing for cervical precancer screening.In response to calls by the World Health Organization for cervical precancer screening services in low-resource settings to lean toward HPV DNA testing, a number of testing platforms have been made available. This study aimed to evaluate the operational parameters of four HPV testing systems in previous ( Cervical cancer is the fourth commonest malignancy among women worldwide and constitutes a significant public health problem, with an estimated 85% of incident cases occurring in the developing world . In GhancareHPV ; the GeneXpert HPV test ; the AmpFire HPV system ; and MA-6000 , which were introduced at our center, the Cervical Cancer Prevention and Training Center (CCPTC), Battor, Ghana and are being considered in this study.A variety of molecular methods exist for the detection of oncogenic HPV and it is generally accepted that persistent positivity is essential for cervical carcinogenesis . HPV DNAcareHPV have been made available https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  17 Jul 2023AttachmentRebuttal_Four_Tests.docxSubmitted filename: Click here for additional data file. 8 Aug 2023Evaluating operational parameters of the careHPV, GeneXpert, AmpFire, and MA-6000 HPV systems for cervical precancer screening: Experience from Battor, GhanaPGPH-D-22-02127R1Dear Dr Essel,We are pleased to inform you that your manuscript 'Evaluating operational parameters of the careHPV, GeneXpert, AmpFire, and MA-6000 HPV systems for cervical precancer screening: Experience from Battor, Ghana' has been provisionally accepted for publication in PLOS Global Public Health.Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.globalpubhealth@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.Best regards,Natalia M. Rodriguez, PhD, MPHAcademic EditorPLOS Global Public Health***********************************************************Reviewer Comments :


Rates of firearm suicide have increased among women Veterans. Discussing firearm access and reducing access to lethal means of suicide when suicide risk is heightened are central tenets of suicide prevention, as is tailoring suicide prevention strategies to specific populations. While research has begun to explore how to optimize firearm lethal means safety counseling with women Veterans, there is limited knowledge of women Veterans' perspectives on including their intimate partners in such efforts. This gap is notable since many women Veterans have access to firearms owned by other household members. Understanding women Veterans’ experiences and perspectives regarding including their partners in firearm lethal means safety conversations can provide important information for tailoring firearm lethal means safety counseling for women Veterans.Qualitative interviews were conducted with 40 women Veterans with current or prior household firearm access. Interview questions focused on the roles of women Veterans’ partners in household firearm access and storage, as well as women Veterans’ perspectives regarding including intimate partners in firearm lethal means safety counseling. Inductive thematic analysis was performed.collaborative, devalued, and deferential. These types were distinguished via women Veterans’ agency in decision-making related to household firearms, partners’ receptivity to women Veterans’ mental health or trauma histories, and willingness (or lack thereof) of partners to change household firearm access and storage considering such histories. Intimate partner violence was common in the devalued relational subtype.Three relational types characterized how household firearms were discussed between women Veterans and their partners: Findings extend knowledge regarding the context of women Veterans’ household firearm access, including relational dynamics between women Veterans and their partners. The acceptability, feasibility, challenges, and facilitators of including women Veterans’ partners in firearm lethal means safety efforts likely vary for each relational type. For example, in dyads with a collaborative dynamic, incorporating partners may create opportunities for increased firearm safety, whereas including partners in devalued dynamics may present unique challenges. Research is warranted to determine optimal methods of navigating firearm lethal means safety counseling in the presence of each relational dynamic. The Department of Veterans Affairs (VA) has prioritized suicide prevention as its leading clinical priority, and there has been increased recognition and concern regarding suicide among women Veterans  of suicide deaths in 2020 , but more likely to report living in households with firearms that they did not personally own (14.4% vs. 2.2%)  is decided and discussed between women Veterans and their partners. Further, intimate partner violence  is experienced by 60% of partnered women Veterans . We enrolled women Veteran participants in this study between April 2021 and January 2022. Individuals were eligible to participate if they met all of the following criteria: reported self-identifying as a woman or that their birth sex was female; previously served on active duty in the U.S. military; were 18–89 years of age; lived in a household with firearm(s) present and/or personally owned firearm(s) at any point after separating from military service; were eligible to receive VHA services and had used VHA services (ever); had experienced lifetime suicidal ideation and/or suicide attempt(s), as assessed by an abbreviated version of the Self-Injurious Thoughts and Behaviors Interview  to identify a national sample of women Veterans who had enrolled in and used VHA outpatient care. We mailed each an invitation letter inviting them to contact us if interested in participating. We supplemented this recruitment strategy with advertising in VHA facilities and at community events, snowball sampling, and mailing an invitation letter to women Veterans who participated in prior research at our center and agreed to be contacted about subsequent research opportunities. We took a purposeful sampling approach to obtain a sample that was demographically and geographically diverse. Throughout data collection, our team monitored sample characteristics, noting any gaps in sample composition and attempting to address these in subsequent recruitment efforts. Thus, sampling emphasized thematic data saturation  and purposeful sampling. Enrollment concluded after we reached saturation and were satisfied that we had addressed purposeful sampling goals.n = 79). Of those, 43 (54.4%) were eligible and 36 (45.6%) were ineligible. Reasons for ineligibility included not having a history of lifetime suicidal ideation or suicide attempt , lacking a history of personal or household firearm access , never having used VHA care , or currently being mobilized on Reserve duty . Of individuals eligible at screening, 40 (93.0%) participated.Interested individuals were screened for eligibility by phone , who inductively identified a set of codes based on immersing themselves in transcripts and interview notes. Next, the team collaboratively developed an initial codebook that included codes and their definitions, then independently applied the codes to a subsequent set of transcripts and notes. The team met again to collaboratively reconcile coded transcripts and adapt the codebook as needed. Analysis was iterative, re-visiting the data to connect it with emerging insights (Srivastava and Hopwood All 40 participants identified as cisgender women. Participants ranged in age from 24 to 73 (median = 53). As reflected in Table Participants reported military service during Post-Vietnam/Peacetime (50.0%), Desert Storm or Desert Shield (47.5%), Operations Enduring Freedom, Iraqi Freedom, or New Dawn (40.0%), and the Vietnam War (7.5%). Army was the most common branch of service (52.5%), followed by Air Force (22.5%), Navy (15.0%), and Marine Corps (15.0%). The majority (82.5%) held enlisted rank at separation.All participants reported currently (60.0%) or previously (40.0%) having household firearms Table . The samAll participants (100%) reported experiencing lifetime suicidal ideation, and half (50.0%) reported experiencing lifetime suicide attempt(s) Table . Nearly collaborative, devalued, or deferential. Here, we briefly summarize each of these, then describe in greater depth the factors that constitute each relational dynamic, using quotes from women Veterans to describe each.Decisions and discussions between the Veteran and her partner regarding household firearm access and storage could be characterized in three ways, as collaborative. In these cases, women Veterans described having both a voice and a sense of agency in firearm matters, feeling highly involved in decisions about household firearms, whether their own or their partner’s. In these cases, Veterans felt that they could engage in equal, shared decision-making with their partner regarding firearms in the home. They felt that both parties were equal in their ability to express their preferences, needs, and concerns regarding firearm access and storage. Generally, Veterans and their partners in this group both personally owned and had access to household firearms. Further, these collaborative relationships were exemplified by the partner’s willingness to make changes to household firearm access, storage, or use. Such changes seemed to be driven by three types of concerns from the woman Veteran: (1) general apprehensions about household firearms; (2) concern that her mental health or trauma history rendered firearm access a danger to herself; and (3) concerns about the safety of children or grandchildren in the home. These collaborative interactions were characterized by high levels of trust between the woman Veteran and her partner, and these Veterans described their partners as current or potential collaborators in firearm LMSC.For many women Veterans, the role of their partners in household firearm decisions could be characterized as devalued. These interactions were characterized by the Veteran having little to no role in the decision-making process surrounding household firearms, despite having prominent concerns regarding their presence, use, or storage in the home. In such instances, the partner used or stored household firearms autonomously without seeking or considering input from the Veteran. Sometimes, women Veterans in these circumstances voiced repeated objections or concerns, yet there typically were not active discussions about firearms, and partners were unresponsive to the Veteran’s concerns and unwilling to change how firearms were used and stored . The partners of women Veterans in the devalued group most often were the owners of household firearms; however, in a few instances, women Veterans themselves also owned firearms . Partners dismissed, downplayed, or directly contributed to the mental health concerns or trauma histories of the woman Veteran that made firearm access dangerous. Such relationships were often characterized by IPV, with the partner maintaining firearms, in part, as a means of control and intimidation. The presence of children had little impact on changing the status of household firearms. Devalued relational dynamics were characterized by low levels of trust between the woman Veteran and her partner. The involvement of such partners in firearm LMSC was low and perceived by woman Veterans as undesired, inherently problematic, and likely unsafe due to IPV and the partner’s domineering behavior.In stark contrast, many women Veterans described their role in shaping decisions regarding household firearms with their partner as deferential. These relationships were characterized by a high degree of trust, which was paramount. Specifically, the woman Veteran afforded her partner almost unilateral control over household firearms, deferring nearly all decisions about where, why, and how firearms were used and stored in the home. This high level of trust manifested through the Veteran and her partner having nearly unstated, implicit mutual understanding about firearm use and storage. Most typically, the woman Veteran’s partner was the owner of household firearm(s). Despite deferring household firearm decisions to their partners, these women Veterans still felt empowered to voice concerns about their partners’ firearms and to be agentic in doing so if they perceived that they needed to discuss potential changes. For example, these women Veterans expressed that although they were largely satisfied with current household firearm storage practices and use, they were confident that their partner would make changes to household firearms in the future if the woman Veteran voiced concerns due to her mental health, trauma history, or the presence of children  in the home. They indicated that their partners had been (or would be) receptive and open to making changes to how and where they stored or used their firearms. They expressed openness to include such partners in LMSC efforts, due to the high trust that characterized such relationships.Some women Veterans’ attitudes and roles toward household firearms were noted as In what follows, we describe each factor that differentiated relational types in greater detail. These factors provide important insights regarding the context and dynamics of these relationships and how partners may, or may not, be appropriate collaborators in firearm LMSC. Synopses of these factors can be found in Table The first matter to consider is the degree to which a woman Veteran desired to be involved in decision-making regarding household firearms. As reflected by the different relational types, women Veterans were not uniform in their stated desire to be involved in decisions regarding firearms.collaborative group desired active involvement in household firearm decisions and felt highly engaged in discussing household firearms with their partners. For example, a Veteran stated that she and her wife were “pretty much on the same page on where to keep [the firearm] and the security of it,” adding that if she wanted to make changes to how it was stored, her wife “would be open to that as well.” Whether because household firearms tended to be jointly owned, or due to the nature of their relationship with their partner, women Veterans in collaborative relationships desired to be actively involved in decisions regarding how firearms were stored within their homes, both currently and in the future.Women Veterans in the devalued relationships also had a desire to be highly involved in firearm discussions, expressing a keen and sharp drive to be more involved in decisions about how household firearms were used and stored. However, they were largely not afforded this opportunity. In instances in which household firearms were discussed, women Veterans noted that they were often overruled or disregarded. Summing up this tension, one woman explained how it is “so challenging because there’s such a huge dynamic in a relationship when someone has a deadly weapon in the home. And that’s even more so when it's against your wishes. You would prefer for that weapon to not be there, but yet they are, it's still there. And you definitely don’t feel comfortable to speak up.”Women Veterans in deferential to their partner on decisions regarding household firearms. The main distinction between Veterans in the deferential and devalued groups was that women Veterans in the deferential group appeared to be satisfied with this arrangement, as their high degree of trust in their partners led them to defer such decisions to their partners. One Veteran noted that although she trusted her husband and “likes the fact that [his firearms are] in the household where it’s easy to access in case something were to happen,” she generally tries not to get too involved. “I know how to use it, I just don’t wanna touch it,” she explained, later noting how her husband “asks me if I wanna practice or use it real quick to see how everything works. I’m like ‘I know how it works, I’m fine.’”In direct contrast to the high actual or desired involvement of women Veterans in the aforementioned groups, women Veterans in the deferential group were largely Related to their desired level of involvement with household firearms was the extent to which women Veterans had their voices heard (or expected that their perspective would be heard and considered) and had an agentic role in household firearm decisions. If a Veteran wanted to be involved in these decisions, how much was her voice valued? Did she have agency in shaping household firearm use, storage, or accessibility with her partner? These questions highlight further nuances within dyads.Collaborative relationships were predicated on the Veteran having a high degree of agency in such discussions, feeling free to voice her concerns, with partners being receptive and open to discussing and problem-solving such concerns. One woman described this process of mutual understanding and problem-solving. “I just told her because of my mental illness, I can’t trust myself, let alone trust myself with guns. Not that I’m suicidal all the time, I mean I have been suicidal in the past. But at that point, it becomes an impulsive act.” She continued by explaining how “we talked about it and I told her that, and she agreed, and she understands, and she’s doing what she can to keep things safe.”devalued relationships described the opposite: having their voices denied, gaslit, or otherwise ignored. “He just brought [a firearm] home and said ‘I bought a gun today.’ And I said ‘Cool, please don’t shoot me.’ And he put it in his nightstand and that was it,” one woman explained, describing her ex-husband’s ignoring of her objections about having firearms in the home. Further, another Veteran described how, despite having concerns about having firearms in the home, her voice was minimized and disregarded, and her husband “would just do his thing, ‘cause we were living in his house.” One Veteran stated that she had limited agency in the firearm decision-making process, detailing how it was “more of him telling me what to do and me not being in a positive state of mind and just going with it. Just whatever he said, whatever he was doing, I was just kind of like ‘Okay’ and not standing up for myself.” Of note, many Veterans described these instances of having their voiced denied in tandem with instances of IPV. In such instances, firearms were often used against women Veterans as instruments of intimidation, control, and manipulation. For example, when asked about her attempts to discuss firearms with an abusive husband, one Veteran recalled how “whenever we were having an argument, he would go back and check on his guns, take them out and show me he had it, and that pretty much ended the argument, he got his way.”Conversely, Veterans in deferential category expressed that while they did not currently have anything to voice issue about, based on their trusting relationship with their partner, they still felt that they had the ability to voice any future concerns, and that their partner would be receptive and open to such discussions. The ability for women Veterans to express their concerns, have their voices heard, and feel like they had could shape decisions regarding household firearms was a major facet of these relational dynamics and impacted other features described. Nonetheless, as these women Veterans often did not perceive firearm access to be an issue, such conversations were largely hypothetical regarding if either party would engage in any such behaviors . For example, one Veteran shared that while she was currently indifferent to her husband having a firearm in their home, due to his occupation as a security officer, she was confident that if she had posed a need for him to remove it due to any mental health concerns, “he probably wouldn’t have objected to it. A firearm was not a status symbol for him. It was just a tool for the job he had.”Meanwhile, women in the Another factor that women Veterans described was their partner’s response (or lack thereof) to them relaying their mental health concerns or trauma histories . This was another feature that differentiated relational groups.devalued group felt as if their partner did not care when presented with such issues and that their partner was actively contributing to their distress, sometimes intentionally or maliciously. In explaining such a circumstance, one woman disclosed how, despite repeated attempts to convey the dangers of her having access to firearms, her ex-husband continued to keep his firearm loaded and easily accessible. “There were times where he wouldn’t lock it up. It didn’t go well because he liked to have it on him,” she explained. Continuing, she stated how “there would be times that it would be left out and that would be such a trigger for me, it would be almost panic attack level, like ‘you can’t have this out where I can see it.’ And then he got very angry.” Ultimately, the stress “just got to be too much,” and she took matters into her own hands, “selling it behind his back.”Veterans in the collaborative and deferential groups felt as though their partners were (or would be) responsive to their concerns regarding their mental health and trauma histories in relation to household firearm access. For example, a Veteran in a collaborative relationship detailed how she and her partner had worked together to find a solution that worked for them both. “I was battling severe depression and there was a moment I considered using [his firearm]…after that, talking to my ex-husband, we got rid of it.”Conversely, Veterans in both the The impact of children or grandchildren in the home on storage and use of household firearms was another aspect of decision-making between women Veterans and their partners that varied across relational types.collaborative relationships, the presence of children or grandchildren motivated actual, direct changes to household firearms, such as storing them more securely, moving them into gun safes, or even selling firearms that were not considered necessary or of practical use. With children in the home, firearms became a renewed source of discussion. One mother stated that while she and her husband jointly decided to “show them the right way to handle [firearms], let them shoot them, showed them how to clean them,” they both agreed to “never show them any of the combinations or anything about the biometric [safes].” Their logic was simple: “If they’ve been taught, then they’re not curious. And that curiosity is where you get the accidents that happen.”For women Veterans in deferential relationships noted a stark contrast to their firearm perspectives when the focus shifted from themselves to minors in the household. Specifically, these Veterans, who traditionally might be indifferent to such discussions, indicated that they would be highly motivated to engage their spouse or partner to change household firearm storage, access, or use, if they had concerns about minors accessing household firearms. Similar to women Veterans in collaborative relationships, women Veterans in deferential relationships indicated that the presence of children  would motivate changes in household firearm use or storage. As one Veteran explained, “I’m okay with how we store them. But you know, we’re trying to have a family, and should we bring a child into this world or adopt or whatever the means is, we will 100% get safes.” Veterans in these cases stated that such concerns were heard and their partners agreed to use gun safes to prevent unauthorized access.Women Veterans in devalued group at times voiced concerns about household firearms due to the presence of children or grandchildren, this did not result in the partner changing household firearm access or storage. Rather, these women Veterans described how their partners were unresponsive to the potential harm that could result from a child accessing an unsecured firearm. Recalling her repeated attempts to discuss with her ex-husband how household firearms were stored, due to her concerns about her daughter’s safety, one woman Veteran explained, “I’d bring it up periodically, but I always made sure that our daughter, she couldn’t get to them. And she knew the guns were there because [my partner] said ‘You don't go here. I've got guns here that could kill you. Don't you ever go there or else you'll get a spanking.’” In another account, a Veteran described how she had always wanted to improve firearm storage in her home—storing ammunition separately from the firearms, if not removing firearms from the home altogether—for her daughter; yet she was not able to do so because of “fear of him.” In some instances, the only thing these Veterans could do to protect themselves and their children was to move themselves and their children out of the home and out of danger. Following an argument in which her husband “pulled out [a handgun] and set it on the dresser,” one Veteran explained how she felt she had to leave with her child, stating how she “wasn’t gonna waste any more time on this. I called my mom and my sister, and they came and brought us back home.”In contrast, while women Veterans in the Partner willingness to make changes to household firearm storage and use was another differentiating factor. Whether due to the Veteran’s stated concerns about how firearms were stored, in response to mental health concerns, or otherwise, women Veterans described their partner’s willingness to make changes to household firearms.collaborative partners often described their partners as open, willing, and capable of making changes to household firearms based on their feedback. One Veteran recounted an event where she had disclosed her mental health concerns to her husband, and her husband’s subsequent actions in removing firearms from the home. “I just expressed to him my bouts of depression, thoughts of wanting to hurt myself, which wasn’t new to him,” she stated. “I just finally told him, ‘I’m telling you this only because of what I need you to do for me. I don’t really wanna talk about it right now, but I will when I’m ready.’ And that was that. And out of respect for it all, he was like ‘Got it. It’s gone.’” In these collaborative relationships, such partners oftentimes had been actively engaged in reducing the Veterans’ access to firearms, whether by removing firearms from the home or changing how they were stored. One Veteran recalled when she had experienced heightened suicide risk; her partner “didn’t ask me any questions or anything else, and we never talked about it. And when I felt as though all of what I was going through wasn’t gonna come back and kill me in my sleep, I was like ‘Okay, when you get the chance, I need to get that box back from you.’ And that was the extent of the conversation.”Women Veterans with deferential about the current state of household firearms expressed that if they did have concerns, their partners would be willing to make those changes. For these Veterans, these statements were largely hypothetical, rooted in the longstanding trust they had developed with their partners. When asked if her partner would be willing to make changes if she were to be at risk for suicide, one woman explained how she believed he would because “I trust him. But I think it’s the individual and who they trust the most…because not everyone has a husband they trust as much as I trust mine, you know?”.Similarly, women Veterans who were largely devalued relationships, however, expressed that their partners felt little to no obligation to make such changes. Despite repeated pleas to their partners, few women Veterans expressed any real sense that their partner would take steps in changing how firearms would be stored in the home. For example, one Veteran detailed how despite an ex-husband knowing of her history of suicide attempts, he made little effort to change how firearms were stored around their home. “[The pistol] wasn’t locked in there or anything. He was kind of worried that I was gonna kill myself…and when I think back on it, it’s kind of messed up that he was worried about me killing myself but didn’t lock it anywhere.”Women Veterans in Women Veterans in each relational type varied in their desire and preference regarding including their partners in firearm LMSC. Their desire for whether to include their partners in firearm LMSC were largely influenced by their level of trust in their partner, their perceptions of their partner, and their prior experiences discussing firearms with their partner.collaborative relationships expressed a desire to include their partners as collaborators in firearm LMSC. In many instances, their prior positive experiences discussing firearms with their partners, making joint decisions together, and their partner’s supportive responsive to their concerns facilitated this preference. “We talk about firearms a lot and I’m confident and I trust him. I know what his ultimate goal is. It’s for the protection of the family and I trust him,” one Veteran shared, noting that this shared trust and engagement in firearm-related issues would make her partner a valued collaborator in LMSC. Because of this shared trust, she indicated that if she were to be at elevated risk for suicide, she would “talk to (him) about it first…my husband and I are very proactive medically.”Women Veterans in deferential relationships indicated that they would be open to including their partners in firearm LMSC. For example, when asked if her partner would be willing to make changes if she were to be at risk for suicide, one woman explained how she believed he would because “I trust him. But I think it’s the individual and who they trust the most…because not everyone has a husband they trust as much as I trust mine, you know?”.Similarly, women Veterans in devalued relationships, however, expressed no desire to include their partners in firearm LMSC. Rather, they indicated that including their partners in firearm LMSC was undesired, inherently problematic, and likely unsafe due to IPV and the partner’s domineering behavior to themselves, as well as to their children. Thus, women Veterans in devalued relationships clearly indicated that controlling partners and those who use IPV would be unacceptable collaborators in firearm LMSC. Describing a past, devalued relationship, a woman Veterans indicated that she did not view her ex-husband as trustworthy enough to involve in firearm LMSC, due to his unsafe firearm practices and behaviors: “[Having firearms in the home] didn’t feel good, and I made it clear to him that we would have to get rid of all of them if we ever started having children because I didn’t think he’d ever keep it safe,” later detailing how “he would be the one that would leave the safe door unlocked for a minute.”Women Veterans in Reducing access to potentially lethal means of suicide is one of the core tenets of suicide prevention. Encouraging such practices is important when working with women Veterans at elevated risk for suicide, as firearm injury has become the leading method of suicide among members of this population  was acceptable to both. For example, in some instances, partners had helped to reduce the Veteran’s access to firearms during times of heightened suicide risk. Thus, barriers to including collaborative partners in firearm LMSC appear to be low. Consequently, it is unsurprising that women Veterans in collaborative relationships expressed a desire and willingness to include their partners in LMSC. Nonetheless, as we only analyzed data from women Veterans (and not from their partners) in this study, it will be important to also obtain the perspectives of partners who are in collaborative relationships to ensure that they also have the resources needed to support their partners in firearm LMSC.For women Veterans in deferential relationships, including partners in LMSC is likely more important if there are concerns regarding the woman Veteran’s firearm access . This is because women Veterans in such relationships were rarely the owners of household firearms, did not have strong preference on how firearms were used or stored, and did not collaborate with their partners on decision-making regarding household firearms. Rather, they trusted their partners to make household firearm decisions, and thus, tended to defer decisions regarding household firearms to their partners, typically forgoing explicitly discussing and addressing firearm safety with their partners. Yet, these Veterans were open to having such discussions if needed in the future—for example, if mental health concerns or the presence of children in the home would prompt dissatisfaction or concerns regarding household firearms. Several aspects of deferential relationships also support the potential feasibility of including these Veterans’ partners in firearm LMSC, such as these women Veterans’ trust of their partners and the compassion and openness of the partner when the Veteran disclosed prior trauma or mental health concerns. While women Veterans in deferential relationships were confident that their partners would be supportive in changing household firearm storage and access if needed, this was largely hypothetical. Should such conversations progress differently than expected, clinician support in navigating such conversations may be needed.In comparison, for healthcare providers working with women Veterans in Devalued relationships likely pose the most challenges to firearm LMSC. This is due to the lack of shared decision-making between the women Veteran and her partner, power imbalances, IPV, and in such instances, fear among women Veterans to suggest or continue advocating for changes to household firearm access and storage due to prior violence or threats of violence to them or their children. In these circumstances, partners controlled women Veterans’ access to household firearms and dictated decisions about access, use and storage for the entire household, even when doing so was dangerous for both women Veterans and children in the household. When women Veterans voiced their concerns, whether due to their own trauma histories, their mental health, or fear of their children gaining access to firearms, their concerns were ignored, neglected, or minimized. Moreover, some partners used firearms as a means of intimidating their women Veteran partners to get what they wanted . Thus, including partners using these invalidating dynamics in firearm LMSC is likely contraindicated and is inconsistent with women Veterans’ stated preferences. Obtaining couples counseling to address broader relational dynamics may be indicated, although the effectiveness and safety of pursuing this option varies considerably (Karakurt et al. While we suggested clinical considerations for working with women Veterans experiencing each of these relational types, future research is warranted to determine if these are indeed correct and to elucidate evidence-based strategies for preventing suicide by firearm among women Veterans in each of these groups. This is particularly important for women Veterans in relationships where their partner devalues their role in firearm decision-making and where IPV is also present. Another important area for future research, which our team is pursuing, is understanding women Veterans’ partners’ perspectives, experiences, and needs regarding firearm LMSC. This is necessary to obtain a comprehensive understanding of experiences, perspectives, barriers, and facilitators to firearm LMSC between women Veterans and their partners. Lastly, quantitative research to validate and/or refine these three relational types and examine associations with other constructs would be valuable.Study limitations include the focus on women Veterans who used VHA services and had a lifetime history of suicidal ideation and/or suicide attempt, as well as the median age of 53 and low proportion of Veterans with current parenting responsibilities or minors in the home. This may limit the relevance of findings to women Veterans outside of VHA care, without a history of suicidality, and those younger with parenting responsibilities. In addition, while the sample was racially and ethnically diverse, low numbers of Asian American Veterans and the absence of any Pacific Islander Veterans is a limitation, particularly given increasing suicide rates within that population (U.S. Department of Veterans Affairs and Office of Mental Health and Suicide Prevention A critical aspect of preventing suicide by firearm among women Veterans with household firearm access entails understanding the vast range of agency among women Veterans over household firearm decisions, even when they are at elevated risk of suicide. Considering the relational dynamics between women Veterans and their partners may further promote delivery of tailored, appropriate LMSC strategies, especially within the context of IPV.


Background: Many Chinese patent medicines have been reported to show anti-tumor cell effects on cervical cancer. To estimate the comparative effectiveness and safety of Chinese patent medicines for cervical high-risk human papillomavirus (HR-HPV) infection.Methods: Randomized controlled trials (RCTs) of Chinese patent medicines for HR-HPV infection were searched in eight databases until 31 August 2022, and two review authors independently extracted data and assessed the risk of bias. Outcomes concerning efficacy were evaluated as odds ratio (OR) and 95% credible intervals (CrI) utilizing R 4.1.2 and Stata 16.1. The protocol was registered on the International Prospective Register of Systematic Reviews (CRD42022351120).Results: We ultimately identified 60 RCTs that involved 5,951 participants and 8 interventions. Chinese patent medicines combined with recombinant human interferon (rhIFN) have better treatment effects than rhIFN alone. The results showed that Baofukang suppository (BFK) combined with rhIFN is greater for the rate of HR-HPV clearance follow-up at 6 months (SUCRA = 78.16%). Kushen gel (KS) combined with rhIFN ranked first for the rate of HR-HPV clearance after treatment (SUCRA = 90.77%). Furthermore, KS + rhIFN is most likely to be the best intervention for improving the clinical effectiveness rate (SUCRA = 87.39%). Adverse reactions were not statistically significant in BFK + rhIFN versus BFK, BFK + rhIFN versus rhIFN, and BFK versus rhIFN.Conclusion: The combination of Chinese patent medicines with rhIFN may demonstrate a higher efficacy than rhIFN alone in clearing the virus and improving cervical symptoms. Weighing with the clinical comprehensive efficacy, BFK + rhIFN and KS + rhIFN maybe the optimal treatments for cervical HR-HPV infection. However, more high-quality randomized controlled trials are needed in the future to further confirm the efficacy and safety of proprietary Chinese medicines for cervical HR-HPV infection. Cervical cancer is the second largest malignant tumor in female malignancy after breast cancer In 2021, the International Federation of Gynecology and Obstetrics (FIGO) proposed tertiary prevention measures for cervical cancer, but mainly for uninfected people and people who have already developed cervical intraepithelial neoplasia (CIN) 2 and CIN 3 At present, local medicines with good effects at home and abroad still cannot meet the clinical needs, Chinese patent medicine combined with interferon seems to be expected to improve the long-term efficacy of HR-HPV infection. There are literatures report on systematic reviews of proprietary Chinese medicines alone or in combination with recombinant human interferon for the treatment of HR-HPV infection, such as Baofukang suppository (BFK) Supplementary S1. The protocol was registered on the International Prospective Registration of Systematic Reviews (PROSPERO) (Number CRD42022351120). There was no ethical approval or consent required for any of the analyses because they were based on previously published studies.The procedure of current NMA was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines “NMA extended version” Supplementary S2. Further eligible studies were identified by manually searching the reference lists of relevant meta-analyses and review articles.The randomized controlled trials (RCTs) of Chinese patent medicine alone or in combination with recombinant human interferon for HR-HPV infection included were recruited through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Chinese Biomedical Databases (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang data from the start of database construction until August 31, 2022. Medical Subject Heading (MeSH) and keyword search terms included were “Chinese herbal”, “Traditional Chinese Medicine”, “Chinese patent medicines”, “high-risk human papillomavirus infection”, “high-risk HPV infection”, “cervical intraepithelial neoplasia”. Besides, the searched Chinese patent medicines were all listed in the Catalogue of Drugs for Basic National Medical Insurance (The 2018 Edition). The English database search strategy was provided in We included published RCTs based on the predetermined selection rules that met the following PICOS criterion:1) Population: Women diagnosed with oncogenic HR-HPV positive but cytology negative or cytology-atypical squamous cells of undetermined significance (ASC-US), or low-grade squamous intraepithelial lesions (LISL), or CIN 1. The definition, screening of HR-HPV and cervical cytology was according to American Society for Colposcopy and Cervical Pathology (ASCCP) Intervention: The experiment group involve Chinese patent medicines combined with recombinant human interferon, Chinese patent medicines only. Both Chinese patent medicines and recombinant human interferon are transvaginal medications.3) Comparison: The control group consist of recombinant human interferon alone or Chinese patent medicines.4) Outcomes: The primary outcome was the rate of HR-HPV clearance follow-up at 6 months . The secondary outcomes were the rate of HR-HPV clearance after treatment and clinical effectiveness rate.5) Study design: We confined our study design to RCTs published with Chinese or English restriction.Studies not adhering to the inclusion criteria were excluded. Other exclusion criteria were:1) Nonrandomized controlled studies such as case-control studies, cohort studies.2) Trials not including the relevant outcomes.3) Trials that did not clearly identify HR-HPV.4) Participants with high-grade CIN 2, CIN 3.5) Data not available or cannot be extracted.6) Interventions include surgery or physiotherapy.7) The duration of treatment is more than 6 months or less than half a month.8) Sample size of the experiment group or control group is less than 10.Two investigators (BCL and MJ) screened the titles, abstracts and full text of retrieved citations independently to identify potentially eligible trials. Any disagreements were discussed between researchers until a consensus was reached. We implemented data a extraction form the collection relevant data for included trial. The following information was recorded from the included RCTs: basic publication information , characteristics of the participants , intervention, intervention duration and outcomes.Two investigators (BCL and MJ) independently conducted quality assessment. Any disagreement was resolved through discussion or judged by an expert as a third author (WSB). We assessed risk of bias of individual studies using the Cochrane Risk of Bias Tool We used GRADE  to evaluate the quality of the evidence for each outcome measure. For direct evidence, we evaluate the quality from five aspects  2, with I2 < 50% indicating no statistical heterogeneity The key assumptions of a network meta-analysis are transitivity, homogeneity and consistency. To determine whether a network meta-analysis was appropriate, the clinical setting and characteristics of trials  reporting each drug class were evaluated. To determine the degree of fit of the model, the deviance information criterion (DIC) between the fixed-effect and random-effect models was used In order to demonstrate direct and indirect comparative relationships among different interventions, we developed evidence networks Figure 1. All of the 60 RCTs were published as Chinese language articles from 2011 to 2022. All the eligible Chinese patent medicines and rhIFN were taken vaginally, and the duration of intervention was from 1 to 3 months. A reference list of the included RCTs was shown in Supplementary S3. We considered a network meta-analysis to be appropriate due to the comparability of patients involved, outcome measures, inclusion criteria, and exclusion criteria. The detailed characteristics of 60 included researches were demonstrated in Supplementary S4. More details of the Chinese patent medicines product  were presented in Supplementary S5, which is convenient for gynecologists and pharmacologists to acquire comprehensive information of the included Chinese patent medicines.We identified 1,252 records from the initial title and abstract screening and retrieved and reviewed 107 reports in full text. We retrieved relevant articles by hand-search to ensure we didn't miss eligible research by omitting the electronic database. We found one RCT Supplementary S6. All of the evidence quality was low or very low. Supplementary S7-S9 presented the GRADE assessment for three outcomes.Most trials (51.67%) described the stochastic methods in detail as random numbers or random lottery. None of those trials mentioned blinding of participants and personnel. All trials reflected a low risk of bias in incomplete outcome data and other biases with sufficient original data. The selection and reporting bias of all studies were unclear risk. Briefly, the risk of bias was moderate in most of the evaluation entries. Full details regarding risk of bias for each RCT were shown in Figure 2 presented the results of the pairwise meta-analysis and heterogeneity estimates. The results of the pairwise meta-analysis showed that four Chinese patent medicines  compared with rhIFN were better than only rhIFN for the HR-HPV clearance rate and the clinical effectiveness rate. BFK + rhIFN was better than only BFK for the HR-HPV clearance rate after treatment and the clinical effectiveness rate. SZJ was worse than rhIFN for the HR-HPV clearance rate and the clinical effectiveness rate. Adverse reactions were not statistically significant in BFK + rhIFN versus BFK, BFK + rhIFN versus rhIFN, and BFK versus rhIFN.Figure 3. Briefly, all outcomes were recombinant human interferon-centric, with the rate of HR-HPV clearance follow-up at 6 months with no closed loop, and for the other two outcomes with one closed loop. Supplementary S10 presented the DIC values and I-square of the fixed-effect model and random-effect model. The DICs of the rate of HR-HPV clearance after treatment and clinical effectiveness rate were similar, and the rate of HR-HPV clearance follow-up at 6 months was smaller in the random-effect model. Therefore, the random-effect model of the three outcomes was used for data analysis in this study. There was no statistical heterogeneity for three outcomes with I2 < 50%.The networks were presented in Figure 3. The results of the network meta-analysis indicated that BFK + rhIFN , SJZ + rhIFN , KS + rhIFN , rhIFN  were better than SJZ. There was no statistically significant difference between the other outcomes (see in Table 1). According to the ranking probabilities of Table 1 and Supplementary S11, BFK + rhIFN (SUCRA = 78.16%) was the first-rank combination in improving the HR-HPV clearance rate follow-up at 6 months, followed by SJZ + rhIFN (SUCRA = 75.40%) and KS + rhIFN (SUCRA = 73.17%).There were 6 interventions, of which rhIFN  was the most studied, followed by BFK + rhIFN . The network plot for the primary outcome of the rate of HR-HPV clearance follow-up at 6 months appeared in Figure 3). According to SUCRA probability results (Table ), KS + rhIFN was the most likely to become the best option for improving the HR-HPV clearance rate after treatment (SUCRA = 90.77%), followed by BFK + rhIFN (SUCRA = 72.15%) and SJZ + rhIFN (SUCRA = 70.04%).There were 24 RCTs reported the rate of HR-HPV clearance after treatment including 8 interventions , which was higher in KS + rhIFN , BFK + rhIFN , ZMK + rhIFN , SJZ + rhIFN  than in those using only rhIFN (see in Table 3). On the basis of SUCRA probability results (Table ), KS + rhIFN (SUCRA = 87.39%) was the optimum therapeutic measure in improving the clinical effectiveness rate, BFK + rhIFN (SUCRA = 78.61%) was number two, and ZMK + rhIFN (SUCRA = 75.78%) was the third.A total of 11 RCTs reported the clinical effectiveness rate  (p > 0.05), indicating that the results were reliable.The funnel plot of the three main results shows the publication bias in The results of this Bayesian network meta-analysis included 60 RCTs to assess the effects of 8 interventions on three outcomes in people with HR-HPV infection. From the results of network meta-analysis, it can be seen that BFK + rhIFN showed the best effect on long-term HR-HPV clear and KS + rhIFN had the best clinical efficacy. In addition, BFK + rhIFN did not appear to increase adverse effects. In summary, the results of this network meta-analysis have certain enlightenment significance for the clinical application and development of traditional Chinese medicine in the prevention and treatment for HR-HPV infection.HPV is a small non-enveloped long double-stranded circular DNA virus, and the expression of viral coding genes E6 and E7 in host cells is a key factor in the occurrence of cervical cancer. Viral DNA integrates E6 and E7-based gene fragments into host cell DNA and activates E6 and E7 gene fragments that regulate virus growth, allowing them to transcribe without restriction, resulting in changes such as immortalized host cells and the evolution of malignant cells In 2021, the World Health Organization's (WHO) “WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition” specifically emphasized and recommended HPV-DNA testing as the preferred method for cervical cancer screening. In nations that have implemented cytology-based screening and treatment programs, the mortality rate associated with cervical cancer has decreased by a factor of five over the past 50 years In recent years, Chinese patent medicines have been widely used for cervical HR-HPV infection. According to studies conducted on cells and animals, Chinese medicine inhibits the expression of HPV16 E6 and E7 genes, regulating immune function For the primary outcome, BFK + rhIFN ranked first (SUCRA = 78.16%). Baofukang suppository, a Chinese medication with a long history of usage for treating gynecological illnesses, has been consistently reported in recent decades that its combination with recombinant human interferon-2b is effective for the treatment of cervical HPV infection. A meta-analysis reported that the HPV clearance rate and total effective rate of the combination of BFK and interferon were superior to those of interferon alone KS + rhIFN performed the best for improving the rate of HR-HPV clearance after treatment (SUCRA = 90.77%) and the clinical effectiveness rate (SUCRA = 87.39%). The main component of KS is matrine, which has antibacterial, anti-inflammatory, insecticidal, itching, antipyretic, analgesic, immunomodulation, antitumor, and other pharmacological effects Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV type, detection method, treatment method, and minimum HPV post-treatment testing interval. Overall, HPV infection tended to gradually clear after CIN treatment for the different treatment modalities Of the included literatures, only BFK, rhIFN, and BFK + rhIFN mentioned the occurrence of adverse events. Most adverse reactions are related to the sensitivity of the cervical tissue caused by the patient's hormone levels, which can disappear on their own without serious reactions such as local infection and cervical injury. Due to the limitations of the literature, it is not yet possible to compare the safety of proprietary Chinese medicines, and more trials observing the safety indicators of proprietary Chinese medicines will be needed in the future to verify this.The combination of Chinese patent medicines and recombinant human interferon performs well in clinical efficiency and HR-HPV clearance rate, thereby providing guidance for the clinical treatment of HR-HPV infection. For patients with a long-term infection and weakened immunity, a combination of BFK and recombinant human interferon may be considered. If cervical symptoms are evident, KS combined with recombinant human interferon may be considered. However, these results must be interpreted cautiously.The first network meta-analysis of different Chinese patent medicines for cervical HR-HPV infection was conducted to provide evidence to support and create traditional Chinese medicine guideline recommendations. We conducted detailed literature reviews and screening, and independently extracted data to ensure that our results were comprehensive and rigorous based on the same criteria. We rigorously conducted subgroup analyses with different time nodes to explore the efficacy of proprietary Chinese medicines at different detection time nodes.However, our network meta-analysis has some limitations. First, all included trials were at high or unclear risk of bias, making the quality of evidence low or very low across all comparisons. Second, the duration of HR-HPV infection, the evaluation criteria for clinical efficacy vary greatly in different trials, and some studies did not mention more details. We recognized that there would be heterogeneity in definitions between trials. Third, there will be some limitations on the external adaptability of the findings, as all the studies were conducted in China. In view of the imperfect design scheme of the included literature, it is recommended that forthcoming randomized controlled trials provide comprehensive descriptions of randomization, allocation concealment, and blinding. Furthermore, the correlation between the duration of treatment of Chinese patent medicines, the follow-up time after treatment, and the rate of negative conversion is a clinically significant matter, and future research can increase the reports in this regard.Chinese patent medicines combined with rhIFN can be more effective than rhIFN alone in clearing the virus and improving cervical symptoms. In terms of clinical efficacy, BFK + rhIFN and KS + rhIFN may be the best treatments for cervical HR-HPV infection. However, due to the poor methodological quality of the included trials, our conclusions should be carefully interpreted. More high-quality randomized controlled trials are required in the future to confirm the efficacy and safety of proprietary Chinese medicines for cervical HR-HPV infection.Supplementary information and tables.Click here for additional data file.