Sexually transmitted infections and the HPV-related burden: evolution of Italian epidemiology and policy.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities.

Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model.

Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17ß-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Health related quality of life and its predictive factors on cervical cancer patients in two teaching hospitals, Addis Ababa, Ethiopia.

BACKGROUND: Cervical cancer is the second most prevalent and the leading cause of cancer related deaths among Ethiopian women; and about three fourth are diagnosed at advanced stages. Cervical cancer can affect the health-related quality of life (HRQOL) in multiple ways. The main aim of this study was to describe the HRQOL of cervical cancer patients and the predictive factors using validated tools. METHODS: Institution based cross-sectional study was conducted among 264 cervical cancer patients using the validated Amharic version of European Organization for Research and Treatment of Cancer (EORTC) modules; QLQ-C30 and QLQ CX24. Descriptive statistics were used to summarize the raw data. One way ANOVA was used to determine the significance of mean differences between the dependent and independent variables. Binary and multivariable regression analysis were used to measure the association between Global Health Status and independent factors. The level of significance was set at p-value < 0.05. RESULTS: On EORTC QLQ-C30 scales, the mean Global Health Status (GHS) was 42.57 ± 23.31. The least and highest affected functions were physical and social, mean (SD) = 76.39 ± 23.24 and 50.40 ± 32.19, respectively. The financial difficulty was the most affected among the symptom scales, 57.83 ± 35.34. Only physical function and financial difficulty have shown an independent association with GHS, (AOR = 0.21, 95% CI = 0.05-0.84), (AOR = 0.21 95% CI = 0.07-0.59), respectively. Illiterate, can read and write, were among the predictor factors that showed an independent association with the Global Health Status. Among the EORTC QLQ-CX24 symptom scales, the highest affected score was for sexual worry, mean (SD) = 51.81 + 32.197. CONCLUSIONS: In an effort to improve the Global Health Status of cervical cancer patients in Ethiopia; physical function and financial difficulty should be the priority areas. The Illiterate and those who lack formal education need due attention in order to improve the health-related quality-of-life.

Risk of progression of cervical intraepithelial neoplasia grade 2 in human papillomavirus-vaccinated and unvaccinated women: a population-based cohort study.

BACKGROUND: Many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option among younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment increases the risk for preterm birth in subsequent pregnancies. However, early identification of women at increased risk for progression to cervical intraepithelial neoplasia grade 3 or worse is important to ensure timely treatment. Because women who have received a human papillomavirus vaccine have a lower risk for cervical cancer, they may have a lower risk for progression of untreated cervical intraepithelial neoplasia grade 2 to cervical intraepithelial neoplasia grade 3 or worse. OBJECTIVE: This study aimed to investigate if women who received a human papillomavirus vaccine and who are undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are less likely to progress to cervical intraepithelial neoplasia grade 3 or worse when compared with women who did not receive the vaccine. STUDY DESIGN: We conducted a population-based cohort study in Denmark using data from national health registers. We identified all women aged 18 to 40 years who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 from January 1, 2007, to December 31, 2020. Women with a previous record of cervical intraepithelial neoplasia grade 2 or worse, hysterectomy, or a loop electrosurgical excision procedure were excluded. Exposure was defined as having received ≥1 dose of a human papillomavirus vaccine at least 1 year before the cervical intraepithelial neoplasia grade 2 diagnosis. We used cumulative incidence functions to estimate the risk for progression to cervical intraepithelial neoplasia grade 3 or worse within 28 months using hysterectomy, emigration, and death as competing events. We used modified Poisson regression to calculate crude and adjusted relative risks of progression during the 28-month surveillance period. Results were stratified by age at vaccination and adjusted for index cytology, disposable income, and educational level. RESULTS: The study population consisted of 7904 women of whom 3867 (48.9%) were vaccinated at least 1 year before a diagnosis of cervical intraepithelial neoplasia grade 2. At the time of cervical intraepithelial neoplasia grade 2 diagnosis, women who were vaccinated were younger (median age, 25 years; interquartile range, 23-27 years) than those who were not (median age, 29 years; interquartile range, 25-33 years). The 28-month cumulative risk for cervical intraepithelial neoplasia grade 3 or worse was significantly lower among women who were vaccinated before the age of 15 years (22.9%; 95% confidence interval, 19.8-26.1) and between the ages of 15 and 20 years (31.5%; 95% confidence interval, 28.8-34.3) when compared with women who were not vaccinated (37.6%; 95% confidence interval, 36.1-39.1). Thus, when compared with women who were not vaccinated, those who were vaccinated before the age of 15 years had a 35% lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse (adjusted relative risk, 0.65; 95% confidence interval, 0.57-0.75), whereas women who were vaccinated between the ages of 15 and 20 years had a 14% lower risk (adjusted relative risk, 0.86; 95% confidence interval, 0.79-0.95). For women who were vaccinated after the age of 20 years, the risk was comparable with that among women who were not vaccinated (adjusted relative risk, 1.02; 95% confidence interval, 0.96-1.09). CONCLUSION: Women who were vaccinated and who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 had a lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse during 28 months of follow-up when compared with women who were not vaccinated but only if the vaccine was administered by the age of 20 years. These findings may suggest that the human papillomavirus vaccination status can be used for risk stratification in clinical management of cervical intraepithelial neoplasia grade 2.

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Diagnosis and rescue of malignant hyperthermia induced by anesthesia during radical surgery in a cervical cancer patient using the National Remote Emergency System: A case report.

RATIONALE: Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics. Due to the infrequency of MH, anesthesiologists often lack sufficient expertise in identifying and managing it, leading to misdiagnosis and inappropriate treatment. There is an urgent need to enhance the diagnosis and management of MH through the utilization of relevant tools. PATIENT CONCERNS: In this case, a 52-year-old woman underwent radical cervical cancer surgery under general anesthesia, with no family or significant medical history. She experienced a gradual increase in end-tidal carbon dioxide (ETCO2) to a maximum of 75 mm Hg and a rise in body temperature from 36.5 to 37.5 °C in a very short period, as well as a blood gas analysis showing a pH of 7.217. DIAGNOSIS: The anesthesiologist immediately used The WeChat applet-based National Remote Emergency System for Malignant Hyperthermia (MH-NRES), and the score was 40, which indicated that the patient was very likely to have MH. INTERVENTIONS: We immediately discontinued sevoflurane and switched total intravenous anesthesia to maintain general anesthesia, with a rapid intravenous infusion of dantrolene sodium. OUTCOMES: The ETCO2 and the temperature quickly dropped to normal, followed by successful completion of the surgery, and the patient was discharged 8 days after surgery. LESSONS: The experience can provide a basis use of MH-NRES and improve the ability of anesthesiologists to deal with intraoperative MH as well as increase the survival probability of patients.

Cervical cancer screening among women with comorbidities: evidence from the 2022 Tanzania demographic and health survey.

BACKGROUND: The aim of this study is to examine cervical cancer screening (CCS) uptake among women living with hypertension and HIV in Tanzania. METHODS: We used the recently released 2022 Tanzania Demographic and Health Survey. The outcome variable assessed in the study was CCS, whereas chronic morbidities constituted the main explanatory variable. Data analysis was based on observations from 6,298 women aged 30-49 years. Multivariable logistic regression models were used to determine the association between hypertension and HIV status, and CCS uptake. The analyses were computed in STATA 18. RESULTS: Out of the 6,298 respondents, only 805 (12.8%) had undergone CCS with higher screening uptake among those living with either one of the disease (28.5%) than among those living with neither hypertension or HIV. The highest proportion was found among those who had ever been diagnosed with hypertension (24.1%) and among women with positive HIV test results (36.7%). There was a significantly higher likelihood of undergoing screening for cervical cancer among women living with at least one of the diseases [AOR = 2.4; 95% CI: 1.4-2.8], compared to those without these conditions. Women diagnosed with hypertension showed increased likelihood of undergoing CCS [AOR = 1.4; 95%CI: 1.1-1.7]. Similarly, women with a positive HIV test result demonstrated higher odds of screening uptake [AOR = 5.2; 95%CI: 4.0-6.7]. CONCLUSION: The study found a positive association between comorbidities and CCS uptake in Tanzanian women. Our findings emphasize the critical importance of ensuring accessibility and adherence to essential screenings for individuals with chronic morbid conditions. Future efforts should focus on strengthening existing integrated services and identifying potential barriers to accessing CCS within these healthcare settings to optimize cervical cancer prevention efforts for individuals with chronic morbidities.

Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.

BACKGROUND: Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. RESULTS: The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. CONCLUSIONS: Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.

The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges.

The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.

Knowledge about cervical cancer in young Portuguese women: a cross-sectional study.

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation. Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention. Materials and methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants. Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge. Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening.

An evaluation of the cost of human papilloma virus (HPV) vaccine delivery in Zambia.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health Week to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine as well as for full immunisation of two doses. METHODS: This work was part of a broader study on assessing HPV programme implementation in Zambia. For HPV costing aspect of the study, with a healthcare provider perspective and reference year of 2020, both top-down and micro-costing approaches were used for financial costing, depending on the cost data source, and economic costs were gathered as secondary data from Expanded Programme for Immunisation Costing and Financing Project (EPIC), except human resource costs which were gathered as primary data using existing Ministry of Health salary scales and reported time spent by different health cadres on activities related to HPV vaccination. Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, provincial, district and health facility levels. Administrative coverage rates were obtained for each district. RESULTS: Findings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest economic cost at USD13.2 per dose and USD 28.1 per fully immunised child (FIC). Overall financial costs for school based delivery were US$6.0 per dose and US$12.4 per FIC. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$47.6 per FIC. The main financial cost drivers were microplanning, supplies, service delivery/outreach and vaccine co-financing; while the main economic cost drivers were human resources, building overhead and vehicles. Nurses, environmental health technicians and community-based volunteers spent the most time on HPV related vaccination activities compared to other cadres and represented the greatest human resource costs. CONCLUSIONS: The financial cost of HPV vaccination in Zambia aligns favourably with similar studies conducted in other countries. However, the economic costs appear significantly higher than those observed in most international studies. This discrepancy underscores the substantial strain placed on healthcare resources by the program, a burden that often remains obscured. While the vaccine costs are currently subsidized through the generous support of Gavi, the Vaccine Alliance, it's crucial to recognize that these expenses pose a considerable threat to long-term sustainability. Consequently, countries such as Zambia must proactively devise strategies to address this challenge.

Understanding effective post-test linkage strategies for HIV prevention and care: a scoping review.

INTRODUCTION: Following HIV testing services (HTS), the World Health Organization recommends prompt linkage to prevention and treatment. Scale-up of effective linkage strategies is essential to achieving the global 95-95-95 goals for maintaining low HIV incidence by 2030 and reducing HIV-related morbidity and mortality. Whereas linkage to care including same-day antiretroviral therapy (ART) initiation for all people with HIV is now routinely implemented in testing programmes, linkage to HIV prevention interventions including behavioural or biomedical strategies, for HIV-negative individuals remains sub-optimal. This review aims to evaluate effective post-HTS linkage strategies for HIV overall, and highlight gaps specifically in linkage to prevention. METHODS: Using the five-step Arksey and O'Malley framework, we conducted a scoping review searching existing published and grey literature. We searched PubMed, Cochrane Library, CINAHL, Web of Science and EMBASE databases for English-language studies published between 1 January 2010 and 30 November 2023. Linkage interventions included as streamlined interventions-involving same-day HIV testing, ART initiation and point-of-care CD4 cell count/viral load, case management-involving linkage coordinators developing personalized HIV care and risk reduction plans, incentives-financial and non-financial, partner services-including contact tracing, virtual-like social media, quality improvement-like use of score cards, and peer-based interventions. Outcomes of interest were linkage to any form of HIV prevention and/or care including ART initiation. RESULTS: Of 2358 articles screened, 66 research studies met the inclusion criteria. Only nine linkage to prevention studies were identified (n = 9/66, 14%)-involving pre-exposure prophylaxis, voluntary medical male circumcision, sexually transmitted infection and cervical cancer screening. Linkage to care studies (n = 57/66, 86%) focused on streamlined interventions in the general population and on case management among key populations. DISCUSSION: Despite a wide range of HIV prevention interventions available, there was a dearth of literature on HIV prevention programmes and on the use of messaging on treatment as prevention strategy. Linkage to care studies were comparatively numerous except those evaluating virtual interventions, incentives and quality improvement. CONCLUSIONS: The findings give insights into linkage strategies but more understanding of how to provide these effectively for maximum prevention impact is needed.

For due or overdue cervical cancer screening, direct or opt-in mailing of HPV self-sampling increased screening at 6 mo vs. education.

SOURCE CITATION: Winer RL, Lin J, Anderson ML, et al. Strategies to increase cervical cancer screening with mailed human papillomavirus self-sampling kits: a randomized clinical trial. JAMA. 2023;330:1971-1981. 38015219.

High burden of human papillomavirus infection among men in Guangzhou, South China: Implications for HPV vaccination strategies.

The epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = -3.882, p < .001), ranging from 31.44% to 52.90%. 28.77% (1075/3737) of men manifested infection with a singular HPV type, predominantly identified as a low-risk type. The age-specific distribution of HPV infections revealed distinctive peaks in the < 25 y age group (47.60%, 208/437) and the 40-44 y age group (44.51%, 154/346). Notably, the positive rate of Chlamydia trachomatis was significantly higher among HPV-positive individuals in comparison to HPV-negatives (16.14% vs. 11.25%, p < .05). Our findings reveal a substantial prevalence of HPV infection among outpatient men in Guangzhou, South China. It is recommended to consider the inclusion of HPV vaccination for adolescent males in national immunization schedules, once an adequate supply of vaccines is accessible.

Inhibition of cytosine 5-hydroxymethylation during progression of cancer precursor lesions in the uterine cervix.

Methylation and hydroxymethylation of cytosine moieties in CpG islands of specific genes are epigenetic processes shown to be involved in the development of cervical (pre)neoplastic lesions. We studied global (hydroxy)methylation during the subsequent steps in the carcinogenic process of the uterine cervix by using immunohistochemical protocols for the detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in paraffin-embedded tissues of the normal epithelia and (pre)malignant lesions. This approach allowed obtaining spatially resolved information of (epi)genetic alterations for individual cell populations in morphologically heterogeneous tissue samples. The normal ectocervical squamous epithelium showed a high degree of heterogeneity for both modifications, with a major positivity for 5-mC in the basal and parabasal layers in the ectocervical region, while 5-hmC immunostaining was even more restricted to the cells in the basal layer. Immature squamous metaplasia, characterized by expression of SOX17, surprisingly showed a decrease of 5-hmC in the basal compartments and an increase in the more superficial layers of the epithelium. The normal endocervical glandular epithelium showed a strong immunostaining reactivity for both modifications. At the squamocolumnar junctions, a specific 5-hmC pattern was observed in the squamous epithelium, resembling that of metaplasia, with the typical weak to negative reaction for 5-hmC in the basal cell compartment. The reserve cells underlying the glandular epithelium were also largely negative for 5-hmC but showed immunostaining for 5-mC. While the overall methylation status remained relatively constant, about 20% of the high-grade squamous lesions showed a very low immunostaining reactivity for 5-hmC. The (pre)malignant glandular lesions, including adenocarcinoma in situ (AIS) and adenocarcinoma showed a progressive decrease of hydroxymethylation with advancement of the lesion, resulting in cases with regions that were negative for 5-hmC immunostaining. These data indicate that inhibition of demethylation, which normally follows cytosine hydroxymethylation, is an important epigenetic switch in the development of cervical cancer.

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study.

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection.

BACKGROUND: To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. METHODS: This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author's Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. RESULTS: Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P < 0.001), showed a lower proportion of menopausal women (38.40% vs. 53.02%, P = 0.0111), a lower proportion of HSIL (40.00% vs. 57.77%, P = 0.001), a higher rate of HPV-16/18 positive (25.60% vs. 17.36%, P = 0.011), a higher rate of contact bleeding (54.40% vs. 21.50%, P < 0.001), lower HDL levels (1.31 ± 0.29 vs. 1.37 ± 0.34 mmol/L, P = 0.002), higher neutrophil counts (median, 3.50 vs. 3.10 × 109/L, P = 0.001), higher red blood cell counts (4.01 ± 0.43 vs. 3.97 ± 0.47 × 1012/L, P = 0.002), higher platelet counts (204.84 ± 61.24 vs. 187.06 ± 73.66 × 109/L, P = 0.012), and a smaller platelet volume (median, 11.50 vs. 11.90 fL, P = 0.002).The multivariable logistic regression analysis showed that age (OR = 0.90, 95% CI: 0.86-0.94, P < 0.001), menopausal (OR = 2.68, 95% CI: 1.38-5.22, P = 0.004), contact bleeding (OR = 4.80, 95% CI: 2.91-7.91, P < 0.001), and mean platelet volume (OR = 0.83, 95% CI: 0.69-0.99, P = 0.038) were independently associated with pathological upgrading from CIN3 to CC after conical resection. CONCLUSION: Age, menopausal, contact bleeding, and mean platelet volume are risk factors of pathological upgrading from CIN3 to CC after conical resection, which could help identify high risk and susceptible patients of pathological upgrading to CC.

Experiences of caring for women with cervical cancer: A qualitative study among male partners in Dar es Salaam, Tanzania.

BACKGROUND: More than three-fourths of cervical cancer cases occur in low- and middle-income countries, with sub-Saharan Africa (SSA) accounting for approximately 25% of global mortality. The significant rise in the prevalence of cervical cancer in SSA amplifies the burden on caregivers, contributing to elevated rates of mental illness, particularly among spouses who provide care. Men who assume the role of caregivers for their partners with cervical cancer encounter unique challenges and substantial adjustments across multiple facets of life, impacting both their own quality of life and that of their partners. Despite this, there is a notable lack of extensive research on the experiences of male partners in caregiving roles, particularly within SSA countries like Tanzania. Therefore, this study aimed to explore the experiences of male partners providing care for women with cervical cancer in Dar es Salaam, Tanzania. METHODS: An exploratory qualitative study was undertaken to explore the experiences of 13 male partners, selected purposively and guided by the principle of saturation. Data gathering employed in-depth interviews utilizing a semistructured interview guide, with subsequent analysis conducted via a thematic analysis approach. RESULTS: Five themes and 13 subthemes were generated, encompassing psychosocial distress, attitudes towards cervical cancer, unity in the provision of care, economic burden, and altered sexual relationships. Participants reported experiencing emotional distress, shifts in social responsibilities, financial challenges, and unfulfilled sexual needs. Moreover, they expressed the need for social, psychological, financial, and sexual and reproductive support. CONCLUSION: This study underscores the numerous challenges encountered by male partners caring for women with cervical cancer, encompassing emotional distress, financial strain, and shifts in social and sexual dynamics. The identified themes and subthemes highlight the intricate interplay of these difficulties and stress the necessity for holistic support systems addressing the social, psychological, financial, and sexual aspects of male partners' experiences. The findings emphasize the importance of designing and implementing comprehensive support programmes tailored to the diverse needs of male partners, ultimately enhancing their quality of life and overall well-being. PATIENT OR PUBLIC CONTRIBUTION: Before the study, the nursing manager assisted in selecting three male partners randomly. These partners were involved in the design of the participants' information sheet, the evaluation of the interview schedule and rooms, and the dissemination of information about the study's purpose to the target population. Their valuable input contributed to improving the participant information sheet, refining data collection procedures and addressing ethical considerations. However, these individuals were not considered study participants. Throughout the study, in-charge nurses in the hospital were informed about the study's goals and helped organize appointments with participants and manage the interview schedule.