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Background/aim: Cervical cancer is the third leading cause of cancer-related death in women worldwide. Nearly all cases of cervical cancer are due to infection with human papillomavirus (HPV). Nowata110 has shown breakthrough therapeutic efficacy in phase II clinical study against plantar warts, with no reported side effects. This study evaluated the effectiveness of Nowarta110 in killing cultured HPV-transformed cancer cells and its anti-cancer effects in mice, using both vaginally engrafted and subcutaneously implanted animal cancer models., Materials and Methods: Nowata110 is a novel compound composed of colloidal silver and fig extract. The cytotoxic properties of Nowarta110 were evaluated on HPV-16 and HPV-18-transformed human cancer cells (ARPE-19/HPV-16 and HeLa cells, respectively). The therapeutic potential of Nowarta110 in vivo was evaluated following the engraftment of ME-180 epidermoid carcinoma cells in the mouse vagina or their subcutaneous implantation. Nowarta110 treatment was initiated when the tumor reached an approximate volume of 65 mm 3 Results: Our data showed that HPV16-expressing human retinal pigmented epithelial cells are susceptible to Nowarta110-induced cell death, with a reduction in cell viability observed at 1% Nowarta110 and a complete absence of viable cells at 5% Nowarta110. In HPV18-expressing HeLa cells, Nowarta110 caused significant and rapid cell death at a dose of 5%, whereas lower doses of 1% did not produce the same effects. The results from animal studies indicated that Nowarta110 effectively induced tumor regression in both the intravaginal and subcutaneous tumor models., Conclusion: Nowarta110 effectively induced cell death in HPV-16 and HPV-18-transformed human cancer cells. It also effectively induced tumor regression in mouse models with intravaginally engrafted or subcutaneously implanted cancer cells. Considering the high prevalence of HPV-induced cervical dysplasia and cancer and the lack of treatment, clinical studies to promote the implementation of Nowarta110 are warranted., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC., Patients and Methods: We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53., Results: All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression., Conclusion: HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression., Methods: We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool., Results: 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance., Conclusion: This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16-positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7., Methods: Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase-polymerase chain reaction. Receiver operating characteristic curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome., Results: The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001)., Conclusion: Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals., Objectives: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval., Study Design: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology., Results: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %., Conclusions: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women., Competing Interests: Declaration of competing interest The authors declare that the study has been conducted in accordance with the principles set forth in the Helsinki Declaration. BS, TR, FS, FA, and GF declare no conflicts of interest regarding the publication of this study. DO and CC are employees of Roche Diagnostics, Portugal. No funding to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus., Methods: We retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient's results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy., Results: The median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26-6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92-22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6-12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6-12 months: p < 0.010, 12-18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers. The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix., Conclusions: Paiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women., Methods: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer., Results: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%)., Conclusion: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Monika Hampl 2024.)

Objective: We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer., Methods: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18., Results: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19)., Conclusion: This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings., (© 2024 John Wiley & Sons Ltd.)

Objective: To determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions., Methods: A cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs., Results: In total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4-80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74-6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15-9.77). GIs were equally present in women with and without CIN3+ lesions., Conclusion: We observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arévalos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To assess the knowledge and acceptability of the human papillomavirus (HPV) vaccine and the associated factors among adolescent girls in public primary schools in Dessie Town, South Wollo, Northeast Ethiopia in 2020., Design, Participants and Methods: This was an institutional cross-sectional study conducted from 1 November to 30 November 2020 among 844 adolescent girls. A systematic random sampling method was used to select participants, who completed a pretested, self-administered questionnaire. Data were entered into EpiData V.4.6 and exported to SPSS V.25 for analysis. A binary logistic regression model identified the contributing factors to HPV vaccine knowledge and acceptance. Adjusted OR (AOR) and 95% CI computed at p<0.05 were used to assess significance levels., Main Outcome Measures: The primary outcomes of interest were knowledge and acceptability of the HPV vaccine., Results: The HPV vaccine is known and acceptable to 47% and approximately 43% of the respondents, respectively. Age (AOR=3.51, 95% CI 1.62 to 7.6), father's educational level (AOR=2.62, 95% CI 1.57 to 4.38) and parent-child communication about sex and reproductive health (AOR=1.94, 95% CI 1.36 to 2.76) were associated with knowledge of the HPV vaccine. Acceptance of the HPV vaccine was significantly influenced by fathers' educational level (AOR=1.88, 95% CI:1.02 to 3.29), knowledge of Pap smear tests (AOR=2.54, 95% CI 1.79 to 3.62) and knowledge of the HPV vaccine (AOR=5.30, 95% CI 3.77 to 7.73)., Conclusion: In this study, there was generally good and high acceptance of the HPV vaccine, respectively, compared with a study conducted in Southwest Ethiopia. The study, however, had limitations in terms of recall bias, assessment of coverage/effectiveness over time and generalisability due to the institutional sample used., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: International guidelines recommend cervical screening cessation at age 50 following two consecutive negative screens. However, many women aged 50 and older in low-income and middle-income countries (LMICs) have not had prior opportunity to screen. We examine the prevalence of cervical dysplasia and cervical cancer stage in Botswana women aged 50+ compared with 30-49, stratified by HIV status., Design: Secondary analysis of data from two prospective cohort studies., Setting: The screening cohort was recruited at health facilities in South East District. The cancer cohort was recruited from the primary public tertiary referral hospital and a private hospital in Gaborone, Botswana., Participants: The screening cohort included 2570 women aged 30 and older recruited from February 2021 to August 2022. Screening eligibility included anyone with a cervix and without a prior history of cervical cancer. The cancer cohort included 1520 patients diagnosed with cervical cancer who sought care at the facilities where recruitment took place from January 2015 to December 2022., Primary and Secondary Outcome Measures: The prevalence of cervical intraepithelial neoplasia (CIN)2+ and cancer stage at diagnosis was compared across age groups, stratified by HIV status. Prevalence ratios were calculated for the association between age and CIN2+/CIN3+via log-binomial regression., Results: The prevalence of CIN2+ was similar between 30-49 years old and 50+, both among women with HIV (WWH, 15.9% and 19.3%, respectively) and without HIV (13.3% and 10.4%, respectively). Similar findings were found when CIN3+ was used as the outcome. There were no statistically significant differences in prevalence ratios (PRs) across age groups for CIN2+ (adjusted PR (aPR) WWH 1.1 (95% CI 0.80 to 1.6); aPR HIV- 0.78 (95% CI 0.45 to 1.4) nor CIN3+ (aPR WWH 1.1 (95% CI 0.70 to 1.6); aPR HIV- 0.81 (95% CI 0.40 to 1.7)). Nearly half of cervical cancer diagnoses were made in women 50+; three-quarters of cases in women without HIV were diagnosed at 50+ years., Conclusions: Our findings demonstrate the prevalence of high-grade cervical dysplasia and cervical cancer remains high beyond age 50 in both women with and without HIV in an LMIC context with high HIV prevalence. Screening women 50+ will allow treatment for cervical dysplasia and may provide early diagnosis of curable cervical cancer. These findings support the rapid introduction of high-performance cervical screening to increase access for women 50+., Trial Registration Number: NCT04242823., Competing Interests: Competing interests: RL reports support for present manuscript—NIH NCI 1K08CA271949-01. AM reports support for present manuscript—UM1TR004408 award through Harvard Catalyst. LB-M reports support for attending meetings and/or travel from MSD. PV reports payment or honoraria from Novartis, Roche, MSD; support for attending meetings and/or travel from MSD, Roche. SG reports grants from National Cancer Institute; grants or contracts from Varian Medical Systems; consulting fees from GenesisCare USA, payment or honoraria from Varian Medical Systems; stock or stock options in Harbinger Health. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937-0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening., (© 2024. The Author(s).)

Background: Human Papillomavirus (HPV) DNA screening was a crucial element in the fight against cervical cancer and had been adopted in many countries, including China. However, the onset of the COVID-19 pandemic in March 2020 disrupted this program significantly., Methods: The aim of this study is to investigate the prevalence and distribution of HPV genotypes among the population undergoing cervical cancer screening during the pandemic period. From January 2017 to December 2022, Peking Union Medical College Hospital gathered 45,496 cervical swabs from individuals undergoing cervical cancer screening. These samples were analyzed to detect fifteen high-risk HPV (HR-HPV) DNA types and a combination of two low-risk HPV (LR-HPV) types., Results: The study revealed an overall infection rate of 11.24% (5,114/45,496), with 11.06% (5,032/45,496) of individuals infected with HR-HPV. The number of HPV screening patients and the infection rates of HPV, HR-HPV, LR-HPV, multiple genotype HPV (M-HPV), and single genotype HPV (S-HPV) during the pandemic were lower than those observed before the pandemic. Moreover, the age group with the highest percentage of infected individuals was under 45-49 years, with HPV52, HPV58, HPV16, and HPV51 being the most prevalent genotypes. Notably, HPV66 emerged as the fifth most commonly detected genotype during the pandemic. Additionally, among the eleven age groups examined, women under 25 exhibited the highest detection rate, with HPV52 and HPV16 infection rates exceeding those observed in the pre-pandemic period., Conclusions: The findings of this study offer significant insights for shaping HPV prevention strategies and enhancing cervical cancer screening initiatives in China following the epidemic., (© 2024. The Author(s).)

Objectives: The World Health Organization supports both the screen-and-treat (ST) approach and the screen, triage and treat (STT) approach to cervical cancer screening using high-risk human papillomavirus (hrHPV) testing. For Uganda, the sequence of hrHPV-ST and hrHPV-STT could be similar, with visual inspection with acetic acid (VIA) after positive hrHPV tests in both. To consider potential tradeoffs (overtreatment in ST versus missed cancer cases in STT), we compared hrHPV-STT with VIA triage (STT-VIA), and STT with HPV 16/18 genotyping risk stratification, to hrHPV-ST for Uganda, in terms of overtreatment, cervical cancer incidence, and life years, for the general female population of Uganda., Methods: A microsimulation model of cervical cancer was adapted. Incremental benefit-harm ratios of STT were calculated as ratios of prevented overtreatment to reduced life years, and to increased cancer cases. Additional scenarios with 20% difference in intra- and inter-screening follow-up between ST and STT were modeled., Results: Both STT strategies resulted in life year losses on average compared to ST. STT-VIA prevented more overtreatment but led to increased cervical cancer incidence and life year losses. STT-G-VIA resulted in better harm-benefit ratios and additional costs. With better follow-up, STT prevented overtreatment and improved outcomes., Discussion: For Uganda, the STT approach appears preferrable, if the screening sequences of hrHPV-based ST and STT are similar in practice. While VIA triage alone would reduce overtreatment the most, it could also result in more cancer cases. Risk stratification via genotyping could improve STT. Potential follow-up differences and resource availability should be considered by decision-makers when planning Uganda's hrHPV-based screening strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sultanov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Human papilloma virus testing is a new method of screening for precancerous cervical lesions. Here we identified factors associated to the positive Human papilloma virus-testing in the context of cervical precancer screening at the Souro Sanou National Teaching Hospital in Burkina Faso., Materials and Method: Conducted from June 2021-May 2022, this was a cross-sectional study, including patients aged between 25 and 55 years-old and screened for precancerous lesions and received HPV-testing at the Department of Gynecology, Obstetrics and Reproductive Medicine (DGORM) of the SSNTH. The proportion of positive HPV-test was calculated, and we identified factors associated to positive HPV-test using logistic regression., Results: Of the 759 patients came for precancerous lesions screening, 559 patients were included. Their mean-age was 38.8 ± 7.9 years-old, 94.3% were from urban area and 50.3% identified as housewives. Regarding the past medical history, it noted: number of gestures (3.2 ± 2.0), parity (2.8 ± 1.9), number of living children (2.8 ± 1.9), having abortion experience (24.0%), age of first-sexual-intercourse(18.6 ± 2.3 years), alcohol (9.1%) and tobacco (1.0%) consumption, sexually-transmitted-infection (27.0%), Human immunodeficiency virus (HIV)infection (5.0%); none had been vaccinated against HPV. Biologically, 16.6% [95% CI: 13.6-20] of the women had a positive HPV-test. The factors significantly associated with positive HPV-test were: occupation in the private sector [OR: 0.06(0.0-0.5); p < 0.001], having a sexually-transmitted-infection [OR: 3.9(2.0-7.7); p < 0.001], age of first-sexual-intercourse [OR: 0.7(0.6-0.9); p < 0.001], sexual-multiple-partnership [OR: 17.5(8.1-39.6); p < 0.001], and HIV status [OR: 13.2(4.4-40.5); p < 0.001]., Conclusion: These results call for health actions through the reinforcement for behavioral change mainly about sexually-transmitted-infections, and for the raising awareness of the population for the screening related to the precancerous lesions and HIV., (© 2024. The Author(s).)

Background: Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines., Methods: Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR., Results: The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine., Conclusion: Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cervical cancer cases continue to rise despite all the advanced screening and preventative measures put in place, which include human papillomavirus (HPV) vaccination. These soaring numbers can be attributed to the lack of effective anticancer drugs against cervical cancer; thus, repurposing the human immunodeficiency virus protease inhibitors is an attractive innovation. Therefore, this work was aimed at evaluating the potential anticancer activities of HIV-PIs against cervical cancer cells. The MTT viability assay was used to evaluate the effect of HIV protease inhibitors on the viability of cervical cancer cells (HeLa) and non-cancerous cells (HEK-293). Further confirmation of the MTT assay was performed by confirming the IC 50 s of these HIV protease inhibitors on cervical cancer cells and non-cancerous cells using the Muse™ Count and Viability assay. To confirm the mode of death induced by HIV protease inhibitors in the HPV-associated cervical cancer cell line, apoptosis was performed using Annexin V assay. In addition, the Muse™ Cell Cycle assay was used to check whether the HIV protease inhibitors promote or halt cell cycle progression in cervical cancer cells. HIV protease inhibitors did not affect the viability of non-cancerous cells (HEK-293), but they decreased the viability of HeLa cervical cancer cells in a dose-dependent manner. HIV protease inhibitors induced apoptosis in HPV-related cervical cancer cells. Furthermore, they also induced cell cycle arrest, thus halting cell cycle progression. Therefore, the use of HIV drugs, particularly HIV-1 protease inhibitors, as potential cancer therapeutics represents a promising strategy. This is supported by our study demonstrating their anticancer properties, notably in HPV-associated cervical cancer cell line.

The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key precancerous conditions in women. This study investigates the influence of different cervical treatment methods on the rate of subsequent vaginal neoplasia. It also considers age and menopausal status as risk factors for higher-grade VaIN and the role of persistent HPV infections in the development of new VaIN cases post-treatment. The cohort consisted of 275 female patients treated for CIN, with a follow-up period of six months including HPV and ThinPrep cytologic test (TCT) testing. The evaluated treatments included laser therapy, cervical conization, loop electrosurgical excision procedure (LEEP), and radical hysterectomy. Statistical analysis was performed using SPSS 26.0 to determine treatment efficacy, the impact of age and menopausal status, and the relationship between HPV clearance and VaIN outcomes. Radical hysterectomy was linked with a higher recurrence of VaIN. Additionally, patients over 50 years old and those who were postmenopausal were significantly more likely to develop more severe VaIN and persistent HPV infections. Persistence of HPV after treatment was linked to a higher incidence of new VaIN cases. High-risk HPV significantly increased the recurrence of VaIN, with no significant link found between TCT results and VaIN severity. Therefore, selecting appropriate cervical lesion treatment, considering the patient's age and menopausal status, and managing HPV infections are essential in preventing and managing the risk and progression of VaIN. Radical hysterectomy showed a distinct increase in VaIN incidence, emphasizing the need for individualized clinical assessments.

Background: Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access., Aim: To determine the prevalence of hrHPV genotypes and cervical lesions' burden in women from the indigenous and marginalized communities of Botswana., Methods: This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68., Results: In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia., Conclusions: Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs., (© 2024. The Author(s).)

Background: High-risk genotypes of Human Papillomavirus are responsible for 90% of cases of cervical cancer worldwide. Inflammation of squamous cells is mainly linked to HPV. In Gabon, HPV is endemic and circulates among the female population. The study aimed to determine the prevalence of HR-HPV genotypes and to investigate the correlation between squamous cell inflammation and HPV viral load in infected women in Gabon., Methods: The cross-sectional study was conducted at Libreville University Hospital Center (UHC) and National Public Health Laboratory from March to May 2024 among 399 women. Two cervical smears were taken. Genotype detection was carried out by multiplex fluorescence real-time PCR in the NPHL virology unit. Cytology was carried out in UHC's anatomic-pathology laboratory. Data were analyzed by SPSS software. Graphs were plotted using Microsoft Excel 2016., Results: The prevalence of Human Papillomavirus was 26.1% (95% CI: 22-30.6). The prevalence of HR-HPV genotypes was 24.8%. The most common HR-HPV genotypes were HPV-16/52/18/35/56/58/53/68. The rate of multiple HPV infections was 29.8% and 95.2% for the HR-HPV infection rate. Viral load was significantly correlated with squamous cell inflammation (r = 0.977 and P = 0.001)., Conclusion: HR-HPV infection remains a concern in women, however early screening is necessary for optimal monitoring and management. HR-HPV viral load is a predictive marker of squamous cell inflammation., (© 2024. The Author(s).)

Cervical cancer is the fourth most common cancer in women worldwide. The vast majority of cervical cancers are associated with human papillomavirus (HPV) infection, but a small proportion of cervical cancers occur independently of HPV infection, with different subtypes having varying rates of occurrence. Despite the presence of false negatives in current testing, improving the accuracy of detection is crucial for studying the pathogenesis of HPV-negative cervical cancer and improving the prognosis of these patients. Existing research suggests that HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer, although the exact mechanism is not yet clear. It is currently believed to be associated with the immune microenvironment, certain tumor gene mutations, and some long noncoding RNAs. This article provides an overview of the latest research progress on HPV-negative cervical cancer, including possible reasons, pathogenesis, pathological features, and clinical characteristics, aiming to provide new insights for diagnosis, treatment, and prognosis improvement., Competing Interests: The authors declared no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Malawi has one of the highest incidence and mortality rates of cervical cancer in the world. Despite a national strategic plan and the roll-out of VIA and screen-and-treat services, cervical cancer screening coverage in Malawi remains far below the national target.Using a nationally representative sample of women enumerated in the Malawi Population-based Impact Assessment (MPHIA) survey we estimated the prevalence and spatial distribution of self-reported cervical cancer screening as a proxy for uptake in Malawi., Methods: MPHIA was a nationally representative household survey in Malawi, targeting adults aged 15 and above, that employed a cross-sectional, two-stage, cluster design. The primary aim of MPHIA was to assess the regional prevalence of viral load suppression and the progress towards achieving the UNAIDS 95-95-95 goals among adults aged 15 and above. The survey was carried out between January 2020 and April 2021. Prevalence of self-reported cervical cancer screening by different characteristics was estimated accounting for the survey design using the Taylor series approach. We used univariable and multivariable logistic regression approaches to examine associations between the prevalence of cervical cancer screening and demographic characteristics., Findings: A total of 13,067 adult (15 years and older) female individuals were surveyed during the MPHIA 2020 to 2021 survey, corresponding to a weighted total of 5,604,578. The prevalence of self-reported cervical cancer screening was 16.5% (95% CI 15.5-18.0%), with women living with HIV having a higher prevalence of 37.8% (95% CI 34.8-40.9) compared to 14.0% (95% CI 13.0-15.0) in HIV negative women. The highest prevalence of screening was reported in the Southwest zone (SWZ) (24.1%, 95% CI 21.3-26.9) and in major cities of Blantyre (25.9%, 95% CI 22.9-29.0), and Lilongwe (19.6%, 95% CI 18.0-21.3). Higher self-reported screening was observed in women who resided in urban regions ((22.7%; 95% CI 21.4-24.0) versus women who resided in rural areas (15.2%; 95% CI 14.0-16.8). Cervical cancer screening was strongly associated with being HIV positive (aOR 2.83; 95% CI 2.29-3.50), ever having been pregnant (aOR 1.93; 95% CI 1.19-3.14), attaining higher education level than secondary education (aOR 2.74; 95% CI 1.67-4.52) and being in the highest wealth quintile (aOR 2.86; 95% CI 2.01-4.08)., Interpretation: The coverage of cervical cancer screening in Malawi remains low and unequal by region and wealth/education class. Current screening efforts are largely being focussed on women accessing HIV services. There is need for deliberate interventions to upscale cervical cancer screening in both HIV negative women and women living with HIV., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Twabi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions., (© 2024. The Author(s).)

Human Papilloma Virus (HPV) is an oncogenic virus and is the most common cause of cervical cancer. HPV has been shown to induce senescence. Cellular senescence is involved in cancer progression and tumorigenesis. Identification and isolation of cells of tumor origin before tumorigeneses is an important step in cancer prevention and treatment. This study aimed to investigate the early cervical atypical senescent cytological preneoplastic change in non-menopausal women. Cervical smears of 121 patients were randomly selected and included in the study which cytopathologically diagnosed as atypical squamous cells of undetermined significance (AS-CUS) in correlation to HPV status, parakeratosis (PK), p16 immunostaining, enlarged Squamous cells nuclei (ES) and inflammatory cells infiltration (ICI). Results revealed that out of the total 121 patients, 32 cases (26%) were positive for high-risk HPV (HR-HPV), 26 cases (22%) were positive for low-risk HPV (LR-HPV) and 63 (52%) were negative for HPV. HPV infections were significantly associated with age groups (p<0.026), PK (p = 0.043), p16 (p = 0.001), ES (p = 0.002) and ICI (p = 0.049). The positive immunostaining expression of p16 was only noticed in two HR-HPV patients. ES cells were found in 9.5% of HPV-negative cases, 27% of LR-HPV cases and 40.5% of HR-HPV cases. High PK cell positivity was seen only in HR-HPV. High ICI scores were seen in 40.6% of HR-HPV patients, 26.9 % of LR-HPV and 17.4 % of negative HPV patients. It was concluded that high PK positivity, high ICI score, positive p16 immunostaining and ES were correlated with HR-HPV in non-menopausal women. These findings could provide potential diagnostic clues for HPV-harboring senescent cells as a strategy for reducing HPV risk of cervical cancer development and identifying the cell of tumor origin, which could be beneficial for improving the utility of senolytic agents and immunotherapy in clinical practice.

Background: Quality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region., Methods: A retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed., Results: The overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a "two-peak" pattern, the peaks of which were observed in the < 21 years group (37.4%) and the 61-65 years group (41.72%). Logistic regression analysis revealed no significant difference in the rate of high-grade lesion positivity between single and multiple high-risk HPV infections. Among patients with a high-grade squamous intraepithelial lesion+ (HSIL+) ThinPrep cytologic test (TCT) diagnosis, HPV58 was the most common type, followed by HPV52, HPV16, HPV39 and HPV53., Conclusions: HPV types 52, 58, 16, 53, and 39 were the most common types in the general female population in Wuhan, and the prevalence of HPV infection varied among different age groups. This study provides a comprehensive overview of the epidemiological characteristics of HPV infection in women, which could support the development of targeted prevention and control strategies for cervical cancer in the region., (© 2024. The Author(s).)

Background: Worldwide, countries are examining whether to implement 1-dose human papillomavirus (HPV) vaccination instead of using 2 doses. To inform policy, we sought to project the population-level impact and efficiency of switching from 2-dose to 1-dose gender-neutral routine HPV vaccination in Canada., Methods: We used HPV-ADVISE, an individual-based transmission-dynamic model of HPV infections and diseases, to mathematically model vaccination programs in 2 provinces, Quebec, a province with high HPV vaccination coverage (around 85%), and Ontario, which has lower coverage (around 65%). We examined non-inferior and pessimistic scenarios of the efficacy (vaccine efficacy of 98% or 90%) and average vaccine duration (lifelong, 30 yr, or 25 yr) of 1 dose compared with 2 doses (98% vaccine efficacy, lifelong vaccine duration). Our main outcomes were the relative reduction in HPV-16 (by sex) and cervical cancers, and the number of doses needed to prevent 1 cervical cancer., Results: Our model projected that 1-dose HPV vaccination would avert a similar number of cervical cancers as 2 doses in Canada, under various scenarios. Under the most pessimistic scenario (25-yr vaccine duration), 1-dose vaccination would avert fewer cervical cancers than 2 doses, by about 3 percentage points over 100 years. All 1-dose scenarios were projected to lead to elimination of cervical cancer (< 4 cervical cancers/100 000 female-years) and to be a substantially more efficient use of vaccine doses than a 2-dose scenario (1-dose v. no vaccination = 800-1000 doses needed to prevent 1 cervical cancer; incremental doses for 2-dose v. 1-dose vaccination > 10 000 doses needed to prevent 1 additional cervical cancer)., Interpretation: If the average duration of 1-dose protection is longer than 25 years, a 1-dose HPV vaccination program would protect those vaccinated during their peak ages of sexual activity and prevent a similar number of HPV-related cancers as a 2-dose program, while being a more efficient use of vaccine doses., Competing Interests: Competing interests:: Chantal Sauvageau is a member of the Quebec Immunization Committee. Sarah Wilson is a member of the National Advisory Committee on Immunization. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids., Methods: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro., Results: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication., Conclusions: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens., (© 2024. The Author(s).)

Background: Variant analysis of distinct HPV types is important from different aspects including epidemiology, pathogenicity, and evolution., Methods: For this reason, the full sequence of the E6 and E7 genes of HPV 58 was examined in 130 HPV 58-infected cervical samples using PCR and sequencing., Results: Our results revealed that three lineages A, B, and D were found in this study; among which the B lineage was more common (91.50%). About sublineages, all samples of the B lineage belonged to the B1 sublineage, and samples that were classified as the A and D lineages were found to belong to the A1 (0.77%), A2 (5.38%), A3 (1.50%), and D2 (0.77%) sublineages. No statistically significant differences were found between lineages and stages of disease or amino acid changes (P > 0.05)., Conclusion: Our results showed that lineage B, sublineage B1, was dominant in Iran. However, more studies with larger sample sizes from different parts of Iran are essential for assessing the pathogenicity risk of HPV 58 lineages in Iranian women with cervical cancer., (© 2024. The Author(s).)

This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens., Competing Interests: VCS Pathology (employer of N.M., M.H.T.K., E.P., E.L., H.T.M.C., M.S., and D.H.), a division of ACPCC, has received research funding or gratis consumables to support laboratory-based research from the following commercial entities in the last 3 years: Abbott, AusDiagnostics, BD, Cepheid, Copan, Qiagen, Roche, Rovers, and Seegene. D.H. is an investigator on the Compass, MaRVE, and SCoPE2(VALHUDES) clinical trials. M.S. is a co-principal investigator (PI) of an investigator-initiated trial of HPV screening in Australia (Compass), which is conducted and funded by the Australian Center for the Prevention of Cervical Cancer (ACPCC), a government-funded health promotion charity. The ACPCC has previously received equipment and a funding contribution for the Compass trial from Roche Molecular Systems USA. M.S. is also a co-PIs on a major implementation program, "Elimination of Cervical Cancer in the Western Pacific," which receives support from the Minderoo Foundation and equipment donations from Cepheid Inc. M.A. was supported by the Horizon 2020 Framework Program for Research and Innovation of the European Commission, through the RISCC Network (Grant No. 847845). Sciensano, the employer of M. Arbyn received funding from the European Society of Gynecological Oncology (ESGO), German Guideline Program in Oncology (German Cancer Aid project), World Health Organization (Geneva, Switzerland, via Agreement for Performance of Work for guidelines on Screening and Treatment of Pre-Invasive Cervical Disease); the European Commission Initiative on Cervical Cancer (EC-CvC) and the VALGENT and VALHUDES projects. D.F., A.L., N.H., and A.H. have no conflicts of interest.

Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: The objective of this study is to evaluate the quality of mobile health (mHealth) applications that promote cervical cancer awareness and provide screening assistance, with an emphasis on apps available on the Google Play Store and iOS., Methods: From December 2023 to February 2024, we assessed mobile applications focused on cervical cancer screening that are available on Google Play and Apple iTunes. The "Cervical Cancer," "Mobile Application," "Pap Test," "Cervical Cancer Guide," "Human Papillomavirus," plus "Cervical Screening are the keywords used to search the applications." Data collection includes features such as application name, pricing, download metrics, invention date, last update, affiliation, online access, login requirements, and notification functionality, which were gathered in Excel. Interrater reliability based on four reviewers' independent judgments, varied from 0.75 to 0.83., Result: In our research, we found 25 apps (16 on the Google Play Store and 9 on iOS). After a thorough review, only 14 relevant apps were included. According to the MARS rating, Rise Against Cancer received the highest score (3.9), followed by FightHPV and Cervical Cancer Forum (3.8). Rise Against Cancer (29), HPV Vaccine (28), and CDC STI Tx Guidelines (28) scored highest in the APPLICATIONS rating system. Hope 4 All and OCI Cervibreast closely matched the statements, meeting seven of the thirteen requirements each., Conclusion: Future app developers should produce user-friendly, often updated mHealth applications that include high-quality cervical cancer awareness and screening content. These apps should provide validated information and pleasant graphic effects.

Background: Cervical cancer has a high incidence and mortality rate, affecting more than half a million women in 2018. Its development is strongly related to high-risk HPV infection. After infection, several cellular molecules are affected, including microRNAs (miRNAs), which are the focus of our study. We aimed to investigate changes in microRNA expression associated with cervical cancer and analyze the biological significance of these changes induced by HPV proteins., Methods: We analyzed transcriptome data retrieved from the NCBI website to investigate miRNA and gene expression in cervical cancer. We evaluated the alteration in expression of miRNAs and genes (between normal tissues and cervical cancer) using the GEO2R tool and selected those with significantly altered expression (p-value < 0.05). The target genes of miRNAs were predicted using the miRNA Pathway Dictionary Database. Subsequently, we created a network of biological pathways affected by miRNA deregulation using Cytoscape software and associated the altered miRNAs with the Hallmarks of Cancer using COSMIC v84., Results: We identified 10 miRNAs and 82 target genes with significantly altered expression levels in cervical cancer that matched the predicted results. In addition, the deregulation of these genes causes changes in 52 biological pathways. These miRNAs affected pathways such as interferon signaling (miR-106b-5p and miR-1183), signaling by interleukins (miR-557, miR-106b-5p, miR-15a-5p, and miR-21-5p), oxidative stress-induced senescence (miR-557 and miR-15a-5p), cell cycle checkpoints (miR-557), transcriptional regulation by P53 (miR-557 and miR-15a-5p), and the exchange of oxygen and carbon dioxide in erythrocytes (miR-15a-5p)., Conclusion: Alterations in miRNA expression play an important role in the pathogenesis of cervical cancer, affecting several biological pathways and Hallmarks of Cancer, such as immune system regulation, cell cycle regulation, and energy metabolism. Thus, their analysis can contribute to the development of diagnostic and prognostic biomarkers and more effective treatments for cervical cancer.

Background To describe the changes in cervical lesions prevalence and high-risk human papillomavirus (HR-HPV) infections from 2012 to 2021, which have never been reported before, to provide direction for the effective implementation of cervical cancer prevention measures. Methods This retrospective study included women aged >25years who received either organised or opportunistic cervical HR-HPV screening from January 2012 to December 2021 in Karamay Central Hospital, Karamay, China. The patients were split into four groups according to age 25-35, 36-45, 46-55 and >55years, respectively. The Joinpoint Regression Program was used to analyse the trends of HR-HPV infection and the detection of cervical lesions. Results Data from 85,429 women revealed a decline in HR-HPV infection rates across all age groups from 2012 to 2021. Although HR-HPV infection rates decreased, cervical lesion detection rates increased, although the proportion of cervical cancer in these lesions declined, likely due to enhanced awareness and HPV vaccination in Karamay. From 2012 to 2021, the prevalence of low-grade squamous intraepithelial lesions was 9.70%, and high-grade squamous intraepithelial lesions was 5.85%. HR-HPV infections were highest in the ≥55years age group, with HPV52 (20.96%) being the most prevalent type. Conclusions In the past 10years, the prevalence of HR-HPV infection has shown a decreasing trend, whereas the detection prevalence of cervical lesions has shown an upward trend among women in Karamay City. Importantly, particular emphasis should be placed on cervical cancer screening in women aged >55years.

Cervical cancer screening is a cornerstone of cervical cancer elimination. Detection of high-risk human papillomavirus (hrHPV) is recommended as the first step in screening provided that the assay used has been adequately validated. The Sansure® Human Papillomavirus DNA Diagnostic Kit is a new assay designed to detect HPV16, HPV18 and 13 other HPV in aggregate. The study aimed to evaluate the intra- and interlaboratory reproducibility of the assay according to international guidelines. Five hundred and fifty cervical residual cell samples from women attending cervical cancer screening were selected from the biobank of the HPV National Reference Centre in Belgium and used in this study. After DNA extraction, HPV was tested using the Sansure® Human Papillomavirus DNA Diagnostic Kit. The lower 95% confidence limit around the general reproducibility of this assay should be greater than or equal to 87%, with κ ≥ 0.50. Five hundred and thirty-three samples had valid results. The Sansure® Human Papillomavirus DNA Diagnostic Kit demonstrated an excellent intra-laboratory reproducibility of 93.8% (95% confidence interval [CI]: 91.4-95.7, κ = 0.85). The interlaboratory reproducibility was 93.4 (95% CI: 91.0-95.4, κ = 0.84). Intra and interlaboratory reproducibility were also excellent at the genotype level. Excluding HPV53 single infection samples from the analyses also resulted in excellent agreement. These data show that the Sansure® Human Papillomavirus DNA Diagnostic Kit is highly reproducible., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Human papillomaviruses (HPVs) represent a diverse group of double-stranded DNA viruses associated with various types of cancers, notably cervical cancer. High-risk types of HPVs exhibit their oncogenic potential through the integration of their DNA into the host genome. This integration event contributes significantly to genomic instability and the progression of malignancy. However, traditional detection methods, such as immunohistochemistry or PCR-based assays, face inherent challenges, and thus alternative tools are being developed to fasten and simplify the analysis. Our study introduces an innovative biosensing platform that combines loop-mediated amplification with electrochemical (EC) analysis for the specific detection of HPV16 integration. By targeting key elements like the E7 mRNA, a central player in HPV integration, and the E2 viral gene transcript lost upon integration, we show clear distinction between episomal and integrated forms of HPV16. Our EC data confirmed higher E7 expression in HPV16-positive cell lines having integrated forms of viral genome, while E2 expression was diminished in cells with fully integrated genomes. Moreover, we revealed distinct expression patterns in cervical tissue of patients, correlating well with digital droplet PCR, qRT-PCR, or immunohistochemical staining. Our platform thus offers insights into HPV integration in clinical samples and facilitates further advancements in cervical cancer research and diagnostics., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: High-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed., Methods: We used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer., Results: RNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer., Conclusion: The successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shao, Shah, Su, Li, Huang, Wang, Wang and Wu.)

Objective: This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020., Methods: This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix., Results: Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears., Conclusion: In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Computer-assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost-effective compared to manual cytology triage in a primary HPV-based cervical screening programme., Methods: Microsimulation model MISCAN-Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost-effectiveness was evaluated by costs per (quality-adjusted) life year ((QA)LY) gained., Results: CAS will be cost-effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost-effective strategy compared to manual cytology triage., Conclusion: As we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost-effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Human papillomavirus (HPV) vaccine is an underutilized tool in cancer prevention. HPV vaccine completion rates in adolescents age 13 to 15 years remain low at 59%. The HPV vaccine can prevent more than 90% of cases of cancer caused by HPV, including cervical, oropharyngeal, anal, penile, vulvar, and vaginal. HPV vaccine is very safe and effective, as demonstrated by numerous large-scale studies. Practice-based strategies can improve vaccination rates, such as having providers give a strong presumptive recommendation for the vaccine, using motivational interviewing for hesitant families, and using electronic health record reminders to prompt providers to offer it, among other interventions. Offering HPV vaccine starting at age 9 years is another evidence-based strategy to improve HPV vaccine completion rates, which has been shown to be acceptable to both providers and parents. [ Pediatr Ann . 2024;53(10):e372-e377.] .

Importance: Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown., Objective: To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective., Design, Setting, and Participants: This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023., Exposure: Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone., Main Outcomes and Measures: Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed., Results: Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations., Conclusions and Relevance: These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Background/historical Perspective: Human papillomavirus (HPV) infections are a significant public health concern as they cause various cancers, including those of the cervix, vulva, vagina, anus, penis, and oropharynx, in both women and men., Summary Integrating the Current Published Literature: Individuals with immune-mediated inflammatory diseases, particularly systemic lupus erythematosus, have an increased risk of developing persistent HPV infection and subsequent precancerous lesions due to their immunosuppression., Major Conclusions: Vaccination and screening for precancerous lesions are 2 central management strategies that must be implemented in patients with immune-mediated inflammatory diseases. Although HPV vaccination has been proven to be safe and effective in these patients, coverage remains low and should be encouraged. Screening for cervical cancer should be more widely implemented in this population, as recommended in guidelines for other immunosuppressed patients., Future Research Directions: Catch-up vaccination, vaginal self-sampling screening for HPV detection, and therapeutic vaccination are new options that should be considered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests., Methods: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests., Results: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method., Conclusions: Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted., (© 2024 Japan Society of Obstetrics and Gynecology.)

Cervical cancer affects women worldwide and is the most common human papillomavirus (HPV)-associated cancer. Carcinogenesis caused by HPV results in specific cancer behavior because of the underlying viral infection. The mechanism and timing of the transformation from viral infection to cancer cells have been elucidated in detail. Treatments for this cancer are based on its characteristics and are being implemented. Moreover, HPV infection is widespread worldwide and is transmitted through sexual activity. Although the HPV vaccination is the most effective strategy of preventing cervical cancer, it is not feasible to vaccinate the entire human population especially in low- and middle-income countries. In order to consider the next step for HPV vaccination, we need to understand the characteristics of HPV carcinogenesis and cervical cancer. Additionally, treatment aimed at preservation of reproductive function in patients with cervical cancer is often required, as the cervix is a reproductive organ and because the disease is more prevalent in the adolescent and young adult generation. Thus, there are still many challenges in the diagnosis, treatment, and prevention of cervical cancer., (© 2024 Japan Society of Obstetrics and Gynecology.)

Purpose: Cervical cancer is a viral-associated tumor caused by the infection with the human papilloma virus. Cervical cancer is an immunogenic cancer that expresses viral antigens. Despite being immunogenic, cervical cancer does not fully respond to immune checkpoint inhibitors (ICI). LIF is a crucial cytokine in embryo implantation, involved in maternal tolerance that acts as an immunomodulatory factor in cancer. LIF is expressed in cervical cancer and high levels of LIF is associated with poor prognosis in cervical cancer., Experimental Design: We evaluated the impact of LIF on the immune response to ICI using primary plasmocytoid dendritic cells (pDC) and macrophage cultures, syngeneic animals and patient-derived models that recapitulate the human tumor microenvironment., Results: We found that the viral proteins E6 and E7 induce the expression of LIF via the NFκB pathway. The secreted LIF can then repress type I interferon expressed in pDCs and CXCL9 expressed in tumor-associated macrophages. Blockade of LIF promotes the induction of type I interferon and CXCL9 inducing the tumor infiltration of CD8 T cells. This results in the sensitization of the tumor to ICI. Importantly, we observed that patients with cervical cancer expressing high levels of LIF tend to be resistant to ICI., Conclusions: Our data show that the HPV virus induces the expression of LIF to provide a selective advantage to the tumor cell by generating local immunosuppression via the repression of type I interferon and CXCL9. Combinatory treatment with blocking antibodies against LIF and ICI could be effective against cervical cancer expressing high levels of LIF., (©2024 American Association for Cancer Research.)

Cervical cancer is preventable due to effective screening to detect pre-malignant lesion, and vaccination against its causative organism namely human papillomavirus (HPV). This review article described current situation of cervical cancer in Malaysia. There is decreasing cervical cancer incidence in the country, with age-standardized rate of 10.3, versus 14.1 and 7.5 per 100 000 for worldwide and high-income countries, respectively. School-based HPV vaccination is part of national immunization since 2010, with yearly coverage rate of 83%-91%. The figure declined during coronavirus disease-19 pandemic due to scarce vaccine supply and movement-control order, resulting in about 500 000 students missing their course, with catch-up program currently onboard. Opportunistic cervical screening program started in 1960s with cervical smear cytology, which is succeeded by HPV DNA screening since 2020. Cervical cytology remains indispensable  screening method in healthcare facility without access to HPV test kit, and used to triage high-risk HPV positive with abnormal cytology that require urgent colposcopy. Computed tomography is the main imaging modality to assess local and distal extent of cervical cancer. Primary surgical treatment for early-stage cancer is performed by trained gynecologic oncologist, with long waiting list for radiation therapy in locally advanced disease due to limited available public facility. There is restricted access to targeted therapy due to high treatment cost. In conclusion, Malaysia is heading toward cervical cancer elimination through rigorous investment in primary and secondary prevention, and increase in public engagement with the support of government policy enforcement., (© 2024 Japan Society of Obstetrics and Gynecology.)

Endocervical gastric-type adenocarcinoma (GAS) is an aggressive type of endocervical mucinous adenocarcinoma characterized as being unrelated to human papillomavirus (HPV) and resistant to chemo/radiotherapy. In this study, we investigated the histology, immunohistochemistry patterns, and molecular characteristics in a large cohort of GAS (n = 62). Histologically, the majority of GAS cases exhibited a distinct morphology resembling gastric glands, although 2 exceptional cases exhibited HPV-associated adenocarcinoma morphology while retaining the characteristic histology of GAS at the invasive front. By immunohistochemistry, Claudin18.2 emerged as a highly sensitive and specific marker for GAS. Additionally, the strong expression of Claudin18.2 in patients with GAS indicated the potential of anti-Claudin18.2 therapy in the treatment of GAS. Other immunohistochemistry markers, including Muc6, p16, p53, Pax8, ER, and PR, may provide additional diagnostic clues for GAS. Quantitative methylation analysis revealed that the overexpression of Claudin18.2 in GAS was governed by the hypomethylation of the CLDN18.2 promoter CpG islands. To further elucidate the pathogenic mechanisms of GAS and its relationship with gastric adenocarcinoma, we performed whole exome sequencing on 11 GAS and 9 gastric adenocarcinomas. TP53, CDKN2A, STK11, and TTN emerged as the most frequently mutated genes in GAS. Mutations in these genes primarily affected cell growth, cell cycle regulation, senescence, and apoptosis. Intriguingly, these top mutated genes in GAS were also commonly mutated in gastric and pancreaticobiliary adenocarcinomas. Regarding germline variants, we identified a probably pathogenic variant in SPINK1, a gene linked to hereditary pancreatic cancer syndrome, in one GAS sample. This finding suggests a potential pathogenic link between pancreatic cancers and GAS. Overall, GAS exhibits molecular characteristics that resemble those observed in gastric and pancreaticobiliary adenocarcinomas, thereby lending support to the aggressive nature of GAS compared with HPV-associated adenocarcinoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cervical cancer prevention in Japan, which had nearly halted due to misinformation, is now recovering through HPV vaccination and screening efforts. While significant progress has been made, much work remains, yet the recent improvements are highly encouraging., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)