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Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment.

Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions., Competing Interests: Disclosure The Author has no financial conflicts of interest to disclose. The opinions expressed by the Author are his own and this material should not be interpreted as representing the official viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent studies have established a correlation between folate levels and the incidence of cervical cancer. Given that Human Papillomavirus (HPV) infection is a primary etiological factor in the development of cervical cancer, the nature of the relationship between dietary folate intake and HPV infection remains an area of ongoing investigation., Methods: To investigate the association between dietary folate intake and HPV infection, this study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Multivariate logistic regression analysis was employed to examine the potential associations. Furthermore, the use of restricted cubic splines (RCS) facilitated the exploration of any non-linear correlations. Additionally, subgroup analyses were used to explore this correlation in different populations., Results: The study encompassed a total of 6747 women aged between 18 and 59 years. For every one mcg increase in folate intake, the incidence of HPV infection is reduced by 1% (OR = 0.99, p<0.05). Besides, folate intake was categorized into quartiles as follows: Q1 (<211 mcg/day), Q2 (211-311 mcg/day), Q3 (311-448 mcg/day), and Q4 (>448 mcg/day). The adjusted odds ratios (OR) for the different folate levels were as follows: Q2: 0.94 (95% CI: 0.76-1.16), Q3: 0.84 (95% CI: 0.67-1.04), and Q4: 0.63 (95% CI: 0.49-0.81). The RCS analysis confirmed a nonlinear relationship between dietary folate intake and HPV infection risk. Notably, a significant inverse association was observed when dietary folate intake exceeded 193.847 mcg/day., Conclusions: In conclusion, the findings of this study indicate a negative association between dietary folate intake and the risk of HPV infection. This association demonstrates a nonlinear pattern, particularly evident at higher levels of folate consumption., Competing Interests: All authors declared that there have no conflict of interest., (Copyright: © 2024 Jin 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.)

Human papillomavirus (HPV), a common cause of sexually transmitted diseases, may cause warts and lead to various types of cancers, which makes it important to understand the risk factors associated with it. HPV is the leading risk factor and plays a crucial role in the progression of cervical cancer. Viral oncoproteins E6 and E7 play a pivotal role in this process. Beyond cervical cancer, HPV-associated cancers of the mouth and throat are also increasing. HPV can also contribute to other malignancies like penile, vulvar, and vaginal cancers. Emerging evidence links HPV to these cancers. Research on the oncogenic effect of HPV is still ongoing and explorations of screening techniques, vaccination, immunotherapy and targeted therapeutics are all in progress. The present review offers valuable insight into the current understanding of the role of HPV in cancer and its potential implications for treatment and prevention in the future., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana., Methods: A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders., Results: A total of 171 participants with a median (interquartile range) age of 40 (31-50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders., Conclusion: These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tsima 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.)

Cervical cancer (CaCx) ranks as the fourth most prevalent cancer among women globally. Persistent infection of high-risk human papillomaviruses (HR-HPVs) is major etiological factor associated with CaCx. Signal Transducer and Activator of Transcription 3 (STAT3), a prominent member of the STAT family, has emerged as independent oncogenic driver. It is a target of many oncogenic viruses including HPV. How STAT3 influences HPV viral gene expression or gets affected by HPV is an area of active investigation. A better understanding of host-virus interaction will provide a prognostic and therapeutic window for CaCx control and management. In this comprehensive review, we delve into carcinogenic role of STAT3 in development of HPV-induced CaCx. With an emphasis on fascinating interplay between STAT3 and HPV genome, the review explores the diverse array of opportunities and challenges associated with this field to harness the prognostic and therapeutic potential of STAT3 in CaCx., 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 Elsevier B.V. All rights reserved.)

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10 -6 -100 μg/mL). We found CSC (10 -3 or 10 μg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2 , PDGFRB , and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Purpose: Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer)., Patients and Methods: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708)., Results: As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined., Conclusions: Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC., (©2024 The Authors; Published by the American Association for Cancer Research.)

Laparoscopic-assisted vaginal radical hysterectomy (LARVH) and abdominal radical hysterectomy (ARH) have been widely applied to treat cervical carcinoma. But LARVH and ARH have not been fully investigated in treating cervical carcinoma after injury associated with injury. This research is intended to provide an up-to-date basis for comparing LARVH with ARH in early stage cervical carcinoma. Comparison between LARVH and ARH in cervical carcinoma was carried out through a combination of related research. Eligible articles from databases such as PubMed and Embase were screened using an established search strategy. This report covered the results of LARVH versus ARH in cervical carcinoma. The average difference and the 95% confidence interval (CI) were used for the combination of consecutive variables. The combination of categorical variables was performed with the odds ratio (OR) 95% confidence interval. Through the identification of 1137 publications, eight of them were chosen to be analysed. Among them, 363 were treated with LARVH and 326 were treated with ARH. Eight trials showed that LARVH was associated with a reduced risk of postoperative wound infection than ARH (OR, 0.23; 95% CI, 0.1-0.55, p = 0.0009). Five trials showed that there was no difference in the risk of postoperative bleeding after surgery (OR, 1.17; 95% CI, 0.42-3.29, p = 0.76). We also did not differ significantly in the duration of the surgery (OR, 1.79; 95% CI, -6.58 to 10.15, p = 0.68). So, the two surgical methods differ significantly only in the risk of postoperative wound infection., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: Obesity is a known risk factor for many types of cancer. However, there is no clear evidence whether overweight and obesity increases the risk of cervical cancer. We investigated the association between body mass index (BMI) and detection of squamous and glandular cervical cancer and precancer., Methods: Based on the Medical Birth Registry, we conducted a nationwide cohort study in Denmark of 384,559 women with BMI ≥18.5 kg/m 2 (pre-pregnancy BMI reported at the start of the pregnancy) having a cervical cytology screening at age 23-49 years within 5 years following the date of childbirth. The cohort was followed for 10 years from the first cervical cytology screening after the childbirth. We assessed absolute risks of cervical lesions according to BMI with the Aalen-Johansen estimator. We conducted Cox proportional hazards regression analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were adjusted for age, calendar year, parity, oral contraception use, HPV vaccination, smoking, country of origin, and education., Results: Overweight and obesity were associated with higher rates of cervical cancer (HR = 1.24, 95% CI 1.04-1.49 and HR = 1.14, 95% CI 0.91-1.43, respectively) and lower rates of cervical precancer detection (HR = 0.88, 95% CI 0.84-0.92 and HR = 0.67, 95% CI 0.63-0.71, respectively)., Conclusions: Higher than normal BMI was associated with higher incidence rates of cervical cancer and lower rates of precancer detection, emphasizing the importance of further research in possible mechanisms behind this association., Competing Interests: Declaration of Competing Interest AU, LTT, USK and KF report no potential conflicts of interest. SKK has received research grants through her research institution from Merck., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China., Patients and Methods: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed., Results: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%., Conclusion: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation., (© 2024. The Author(s).)

Background: Cervical cancer (CC) myths and beliefs can negatively impact women's preventive behaviors, including vaccination against human papillomavirus and having regular screening tests. This study aimed to examine awareness of Palestinian women about myths related to CC causation and investigated factors associated with good awareness., Methods: A national cross-sectional study was conducted to recruit adult Palestinian women from hospitals, primary healthcare facilities, and public areas in 11 Palestinian governorates. A translated-into-Arabic version of the Cancer Awareness Measure-Mythical Causes Scale was used to collect data. Awareness level was determined based on the number of CC myths around CC causation recognized to be incorrect: poor (0-4), fair (5-9), and good (10-13)., Results: A total of 7058 questionnaires were included. Myths unrelated to food were more commonly recognized as incorrect compared to those related to food. The most recognized food-unrelated myth was 'having a physical trauma' (n = 3714, 52.6%), whereas the least recognized was 'using mobile phones' (n = 2238, 31.7%). The most recognized food-related myth was 'drinking from plastic bottles' (n = 2708, 38.4%), whereas the least recognized was 'eating food containing additives' (n = 1118, 15.8%). Only 575 participants (8.1%) displayed good awareness and promptly recognized at least 10 out of 13 myths around CC causation as incorrect. Factors associated with lower likelihood of displaying good awareness of myths around CC causation included living in the West Bank and Jerusalem, being married, widowed or divorced, knowing someone with cancer, and visiting hospitals or primary healthcare centers., Conclusions: A very small proportion of Palestinian women recognized 10 or more myths around CC causes as incorrect. Initiatives addressing CC myths are needed in the Palestinian community., (© 2024. The Author(s).)

Cervical intraepithelial neoplasia (CIN) is a pre-malignant lesion of the cervix of uterus. Several risk factors increased the risk of developing CIN. Purpose of this study was to evaluate the socio-demographic risk factors related to CIN at our setting. This Cross sectional observational study was performed at Colposcopic clinic of Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from 9th November 2017 to 8th May 2018. Overall demographic features of 50 patients of precancerous cervical lesion show that, most of the patients belonged to the age group 30-39 years (46.0%), mean age was 32.7±10.3 years. Maximum numbers of respondents came from rural area (58.0%), followed by urban area (42.0%). Among them house wife- 46.0%, daily worker- 30.0% and illiterate 36.0%, primary level of education 32.6%. Among the patients the poor class 46.0% and 58.0% of the respondents were married at age ≤19 year. Among the respondents, (26.0%) were conceived their first child 1 month after their marriage and 54.0% of the women within 12 months of marriage. In this study multipara were (62.0%). Oral contraceptive pill was taken by (42.0%) of patients. The association of risk factors revealed that betel or tobacco chewing present in 28.0% cases; history of menstrual regulation (MR), dilatation, evacuation and curettage (DE&C), miscarriage were in 26.0% cases, family history of cancer were in 16.0% cases and multiple sexual exposure was in 10.0% cases. Women develop pre-malignant cervical lesions require early treatment. It is recommended that provision of proper health care support, early detection of CIN and proper management, can reduce the fatal outcome of the disease.

Objective: The authors aimed to investigate the prevalence of pregnancy and obstetric outcomes in patients who underwent radical trachelectomy (RT) for early-stage cervical cancer in the Kanto area, Japan., Method: A survey among 113 perinatal centers affiliated with the Kanto Society of Obstetrics and Gynecology was conducted to investigate their experience in managing pregnancies following RT, between 2010 and 2020. The association between preterm delivery (before 34 gestational weeks) and a midtrimester short cervix (<13 mm) was evaluated., Results: The authors retrospectively collected maternal and perinatal data from 13 hospitals. There were 135 pregnancies among 115 women following RT. Of the 135 pregnancies, 32 were miscarriages (<12 gestational weeks: n = 22; >12 gestational weeks: n = 10), and 103 were delivered after 22 gestational weeks. The incidences of preterm delivery before 28 and 34 gestational weeks were 8.7% and 30.1%, respectively. A midtrimester short residual cervix was associated with preterm delivery (P = 0.046)., Conclusion: Since more than 100 pregnancies were recorded after RT in the Kanto area, many physicians had more opportunities to manage pregnancy after RT. Pregnancy following RT is associated with increased risk of preterm delivery, and midtrimester short residual cervix is a good predictor of preterm delivery., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Carcinoma of the cervix is a globally significant cause of morbidity and mortality among women. Concurrent chemoradiotherapy, a standard approach for locally advanced cervical cancer, invariably involves pelvic irradiation. Although this strategy is effective, it inevitably affects the pelvic bone marrow, a crucial hematopoietic site, and leads to hematological toxicity The potential of IMRT to spare bone marrow in pelvic irradiation settings has been an area of significant interest, with the aim to mitigate the hematological toxicity associated with pelvic radiotherapy. Radiotherapy techniques have evolved in terms of conformity and normal tissue sparing. Our study intends to explore the use of BM sparing techniques among patients of carcinoma cervix., Patients and Methods: Twenty patients of carcinoma cervix FIGO Stage IIIB treated with concurrent chemoradiotherapy were selected for this study. The external contour of bones was delineated on planning CT as a surrogate for BM. We generated three plans on a single patient:1. without BM as the dose constraint, namely N-IMRT plan; 2. with BM constraint, namely BMS-IMRT plan; 3. VMAT plan in which BM constraint was given. The dose volume histogram (DVH) for planning target volume (PTV) and organs at risk (OAR) were analyzed. BM parameters: V10, V20, V30, V40, mean, maximum and minimum dose were compared.  Results: PTV coverage was comparable in all techniques. VMAT plans resulted in superior BM sparing compared with N-IMRT plan (P-<0.001) and BMS-IMRT plan (P-<0.001, 0.021 and 0.001 respectively for V20, V30 and V40). VMAT plans had better CI compared with BMS-IMRT (P-0.002) and N-IMRT (P-0.001) plans., Conclusion: Our study adds to the growing evidence that VMAT might be the preferred technique for patients with carcinoma of the cervix undergoing concurrent chemoradiotherapy, as it provides comparable target coverage and better sparing of bone marrow compared to IMRT.

Objective: To describe the long-term outcomes of patients with stage IVA cervical cancer, a rare and deadly disease for which long-term toxicity data are scarce, to guide clinician counseling and survivorship support., Methods: In a retrospective review of a prospectively maintained database, we identified 76 patients with stage IVA cervical cancer with biopsy- or MRI-proven bladder mucosal involvement who received definitive radiotherapy (external beam radiotherapy [EBRT] alone or EBRT plus brachytherapy) with or without chemotherapy at our institution between 2000 and 2020. We used Kaplan-Meier modeling to estimate recurrence-free survival (RFS) and overall survival (OS) and used proportional hazard modeling to identify clinical variables associated with recurrence or survival. We performed actuarial competing risk modeling for severe late toxicity (grades 3 to 5, occurring >6 months of follow-up) and vesicovaginal fistulae (VVF), censoring for pelvic recurrence and death, and made comparisons between potential predictors using Gray's test and binary logistic regression., Results: The median follow-up time was 76 months (interquartile range 58-91). The median OS duration was 35 months (range, 18-not reached), and the 2- and 5-year OS rates were 53.6% and 40.9%, respectively. OS and RFS did not differ significantly between patients who received EBRT alone (N = 18) or EBRT plus brachytherapy (N = 49). Current smoking was a strong predictor of severe late toxicity, whose incidence was 14% at 2 years and 17% at 10 years. The VVF incidence was 24% at 2 years and 32% at 10 years., Conclusion: Patients with stage IVA cervical cancer, even those who receive EBRT alone, can have long-term survival. These patients should be followed closely for late radiation-related toxicity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Importance: Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US., Objective: To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown)., Design, Setting, and Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022., Interventions: Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506)., Main Outcomes and Measures: The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group., Results: The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%])., Conclusions and Relevance: Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT04679675.

Cervical cancer is a global public health problem. It is the second leading cause of death among women of childbearing age worldwide. Several factors, including diet, have been shown to influence the risk of persistent HPV infection and tumor progression. This paper determines the relationship between dietary patterns and cervical cancer. It is an ecological study of multiple groups, based on two national sources: the High-Cost Account and the National Survey of Nutritional Situation of Colombia of 2015. The population consisted of 3472 women aged 35 to 64. The incidence of cervical cancer was used as the dependent variable while the independent variables included food consumption according to established patterns, area of residence, age, physical activity, and BMI, among other variables. The statistical analysis performed through associations between variables was evaluated by multiple linear regression using R2. 38.9% of the evaluated population belonged to the first quartile of wealth, and 76.5% resided in the municipal capital. The incidence of cervical cancer in Colombia was associated with being affiliated to a state-subsidized health regime and having diabetes mellitus. A conservative eating pattern, as well as belonging to a rural area, are evidenced as protective factors. These results invite the need to encourage public policies and promote healthy lifestyles.

Objective: To evaluate the effect on patient outcomes when introducing a novice robotic surgeon, trained in accordance with a structured learning curriculum, to an experienced robotic surgery team treating cervical cancer patients., Methods: Patients with early-stage cervical cancer who were treated with primary robot-assisted surgery between 2007 and 2019 were retrospectively included. In addition to the 165 patients included in a former analysis, we included a further 61 consecutively treated patients and divided all 226 patients over three groups: early learning phase of 61 procedures without structured training (group 1), experienced phase of 104 procedures (group 2), and the 61 procedures during introduction of a novice with structured training (group 3). Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to assess the learning curve effect. Patient outcomes between the groups were compared., Results: Based on RA-CUSUM analysis, no learning curve effect was observed for group 3. Regarding surgical outcomes, mean operation time in group 3 was significantly shorter than group 1 (p < 0.001) and similar to group 2 (p = 0.96). Proportions of intraoperative and postoperative adverse events in group 3 were not significantly different from the experienced group (group 2). Regarding oncological outcomes, the 5-year disease-free survival, disease-specific survival, and overall survival in group 3 were not significantly different from the experienced group., Conclusions: Introducing a novice robotic surgeon, who was trained in accordance with a structured learning curriculum, resulted in similar patient outcomes as by experienced surgeons suggesting novices can progress through a learning phase without compromising outcomes of cervical cancer patients., Competing Interests: Declaration of Competing Interest RPZ is a proctor for robot-assisted surgery in gynaecological oncology on behalf of Intuitive Surgical. All other authors declare they have no conflicts of interests related to the presented research., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The human papillomavirus (HPV) is a well-known oncovirus whose causal link in the occurrence and development of several cancers, such as cervical cancer (CC), has been well established. Indeed, numerous researches depicted the etiological role of HPV in CC pathogenesis in such a way as to develop efficient strategies, including early diagnoses and HPV vaccination, to mitigate HPV infection and CC occurrence. Despite the effectiveness of these strategies in preventing HPV infection, its persistence, and the progression to precancerous lesions and cancers, extensive work that could give a better understanding of other unknown factors favoring oncogenesis is much more needed. In this last decade, scarce or few but crucial and strategic studies have been carried out to improve and deepen our understanding of the etiopathological role of HPV in the progression towards the development of CC. In this review, we highlighted the recent findings on the pathological role of HPV in CC occurrence and the advances in novel adopted strategies to reduce HPV infection and prevent CC occurrence more effectively., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Several studies have shown that male involvement increases the uptake of sexual and reproductive health programmes for improved family health outcomes. The role of men in reducing the burden of cervical cancer has however not been researched in Zimbabwe. It is for this reason that this study explores male support for cervical cancer screening programmes from the perspective of women and health providers in the Gwanda district of Zimbabwe. A qualitative approach that engaged thirty-six women aged 25-50 years in focus group discussions, and twenty-five health providers with different roles in the cervical cancer screening programme in in-depth interviews was used to determine their perspectives on male support for cervical cancer screening. Data were analysed thematically using ATLAS.ti Computer Assisted Qualitative data analysis software. Key findings reflected that men lacked knowledge on cervical cancer and its risk factors and prevention. Subsequently, they engaged in sexual behaviours that increased their partners' risk of acquiring Human Papillomavirus infection, the virtually necessary cause of cervical cancer. Furthermore, men did not provide the necessary emotional and financial support for their women to access screening and treatment. Participants were optimistic that innovative awareness creation strategies and intense, sustained cervical cancer education efforts targeting men could increase male partner support. Involvement of community leaders was seen as crucial in the facilitation of male involvement for programme acceptance and improved uptake of cervical cancer screening. Male involvement is seen as an integral component of the cervical cancer prevention and control programme that has to be implemented in Gwanda district to minimise male partner-related barriers to cervical cancer screening. Further research focusing on men is required to identify specific knowledge gaps that would enable development of appropriate strategies that best involve men in cervical cancer prevention and control interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mantula, Toefy. 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: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments., Methods: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05., Results: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38)., Conclusion: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immunocompromised women are at increased risk of having HPV detected and developing HPV-related diseases such as genital warts, anogenital dysplasia, and cancer. This review aims to summarize the current literature regarding the immunogenicity of the HPV vaccine in immunocompromised women and to discuss whether HPV vaccination may be able to reduce the risk of cervical dysplasia and cancer. HPV vaccination induces an immune response in these women; however, it is unknown whether vaccination is effective in reducing the risk of cervical dysplasia and cancer. Further research is needed.

Background: This review aims to determine the potential role of Merkel Cell Polyomavirus (MCPyV) in the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas., Methods: A PRISMA systematic search appraisal was conducted. The Scopus, Web of Science, PubMed, EMBASE, Google Scholar, and MEDLINE databases for publications in English were searched up to September 2022 for all relevant articles. All articles that have outlined the contributions of the MCPyV to cervical squamous cell carcinomas and adenocarcinomas were included., Results: The six databases produced 6806 articles. Only six articles met the inclusion criteria and were included. The protocol of this review was submitted and registered with the PROSPERO (Code no. CRD42022369197). The total sample size across the articles was 1135; the age of the participants ranged between 18 and 75 years. In addition, the included articles were conducted between 2012 to 2016. All included articles have a cross-sectional design.Furthermore, different kinds of samples were collected in the reviewed articles, namely cervical tissue biopsies, cervical smears, formalin-fixed paraffin-embedded resection specimens, and cervical adenocarcinomas. Moreover, five articles showed no statistically significant association between the MCPyV and cervical squamous cell carcinomas and adenocarcinomas. In contrast, one article revealed a positive association between MCPyV and cervical squamous cell carcinomas and adenocarcinomas., Conclusions: MCPyV could not be associated with the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. Further attention should be given to examining this association, and further studies with a large sample size are recommended to confirm these findings., (© 2023 Hatim M., et al.)

Objective: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer., Methods: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, β = 80%, one sided., Results: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms., Conclusion: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed., Competing Interests: Declaration of Competing Interest Vergote I. as corresponding author declares consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis; Contracted research (via KULeuven) from Oncoinvent AS; Corporate sponsored research from Amgen and Roche and accommodations and travel expenses from Karyopharm, Genmab and Novocure. Van Nieuwenhuysen E. declares consulting/advisory board fees from AstraZeneca, Regeneron; research support from Eli Lilly and travel expenses from Roche and PharmaMar. Casado A. declares consulting or advisory role from Roche Spain, PharmaMar, Eisai, Merck Sharp & Dohme, Eisai (all personal); research funding from PharmaMar (institutional); travel and accommodation support from PharmaMar, Roche, Lilly Spain (all personal); other relationship with Lilly (institutional). Laenen A. declares no conflicts. Lorusso D. declares consultant honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis and PharmaMar; invited member of advisory board from Oncoinvest, Corcept, Sutro; invited speaker and member of advisory boards from AstraZeneca, Immunogen, GSK, Seagen, Genmab; research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar; grants for traveling: AstraZeneca, Clovis Oncology, GSK. Braicu E.I. received research funding from Bayer, Roche Diagnostics, Tesaro, GSK, and AstraZeneca and received personal fees from AstraZeneca, Clovis, GSK, Tesaro, EISAI, RochePharma, and Roche Diagnostics. Guerra-Alia E. has received advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; she has received speaker bureau/expert testimony honorarium from AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis and she received travel/accommodation/expenses from Roche, GSK-Tesaro and Baxter. Zola P. declares consulting fees from Astrazeneca. Wimberger P. has received research funding from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, Lilly, honoraria from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daichii Sankyo. He participates at advisory boards from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead and Daichii Sankyo. Debruyne P.R. received grants from Pfizer (institutional); consulting fees for Advisory Boards from BMS, Merck Pfizer, Ipsen; honoraria for lectures from Bayer; travel support from Janssen; (Substitute) Board Member, Clinical Trials College, Federal Public Service, Kingdom of Belgium; stock or stock options from Alkermes and Biocartis Group NV. Ferrero A declares honoraria from GlaxoSmithKline, Clovis, Astra Zeneca-MSD; invited member of advisory boards from Astra Zeneca-MSD. Muallem MZ received consulting fees from Styker, Intuitive and BD. Garcia-Martinez E. received accommodations and travel expenses from GSK, Roche, MSD and consulting or educational fees from GSK, AstraZeneca, Pharmamar, MSD. Pignata S. has no COI related to this paper. Sehouli J. received consulting fees from Tesaro, Merck/Pfizer, PharmaMar, Clovis Oncology, Eisai, Oncoinvent, AstraZeneca, Roche Pharma, GlaxoSmith, MSD, Novocure; honoraria for lectures from Tesaro, PharmaMar, Clovis, Roche, Vifor Pharma, Novartis Pharma, GlaxoSmith, AstraZeneca, Bayer, PharmaMar, Hexal AG; patents from Roche Pharma, Bayer, GlaxoSmith, Tesaro, AstraZeneca, Clovis and Lilly. Van Gorp T. received grants from Amgen, Roche and AstraZeneca (institutional); consulting fees from AstraZeneca, Eisai Europe, OncXerna Therapeutics, MSD/Merck, GSK, ImmunoGen and Seagen (all institutional); he received travel support from Amgen, Pfizer, Roche, Sanofi-Aventis, Novartis, Roche, Immunogen, MSD, AstraZeneca, PharmaMar and GSK. Gennigens Ch. declares no disclosures for the present manuscript; grants/contracts from AstraZeneca, consulting fees from Ipsen, GSK and MSD; honoraria for lectures etc. from MSD, BMS, Ipsen, Pfizer, Pharmamar, AstraZeneca, GSK; support for meetings and/or travel: Ipsen, Pharmamar, Pfizer, MSD, GSK; participation on data safety monitoring board or Advisory Board: MSD, BMS, Ipsen, AstraZeneca, GSK, Eisai. Rubio MJ. has served on advisory boards for MSD, AstraZeneca, Roche, GSK, Clovis, PharmaMar and received support for travel or accommodation from Roche, AstraZeneca, PharmaMar, MSD and GSK., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives : Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence. Materials and Methods : We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose. Results : The median follow-up period was 15 months (range: 3-120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance. Conclusions : Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.

Background: Cervical cancer is the fourth most common cancer in women, worldwide. Most often, cervical cancer is caused by a human papillomavirus (HPV) infection. A lack of studies concerning HPV knowledge and vaccination among the Lebanese population is noticed. We aim to assess the prevalence of HPV vaccine administration among female university students in Lebanon alongside determining the predictors influencing vaccine uptake. Lastly, knowledge scores concerning HPV and HPV vaccination are also computed., Methods: This is a cross-sectional analytical study. It is an anonymous, online-based, close-ended questions survey conducted between the 24th of February 2021 and the 30th of March 2021. Our questionnaire was addressed to females aged between 17 and 30 years and enrolled in a Lebanese university. The collected data were analyzed using Statistical Package for Social Sciences (SPSS) v.26. We used bivariate analysis to compare the rate of vaccination with different variables. We used the chi-square test for categorical variables and Student's t -test for continuous variables. Logistic linear regression was conducted between the state of vaccination and other statistically significant variables from the bivariate analysis., Results: We have received a total of 454 questionnaires. Among the respondents, only 18.9% had received a minimum of one dose of the HPV vaccine. The mean age of up taking the first dose of the vaccine was 17.5 years. In addition, 48% of the respondents were not willing to take the HPV vaccine during the upcoming year. Barriers to not taking the HPV vaccine were mainly the low levels of knowledge concerning HPV and its vaccine. In the multivariate analysis, three predictors were found to affect the rate of HPV vaccination: university type, paternal educational level, and HPV vaccine knowledge score. In detail, a student enrolled in a public university had 77% likelihood of not being vaccinated. Furthermore, female students with a paternal educational level higher than a university degree had 88% probability of being vaccinated. Finally, every increase in the HPV vaccination knowledge of one point increased the likelihood of being vaccinated by 37%., Conclusion: A low vaccination rate among female university students in Lebanon was noticed in our study. In addition, a lack of HPV and HPV vaccine knowledge was found in our population. An awareness campaign alongside public vaccination programs is recommended in order to accomplish higher rates of HPV immunization., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Joey El Khoury et al.)

Public awareness of the link between the human papillomavirus (HPV) and cervical cancer has declined over the past several years. The findings also reveal low awareness of HPV's connection with other cancers, including anal, oral, and penile, highlighting an urgent need for educational campaigns targeting medical professionals and the public., (©2023 American Association for Cancer Research.)

Advanced gynecologic cancers have historically lacked effective treatment options. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration for the treatment of cervical cancer and endometrial cancer, offering durable responses for some patients. In addition, many immunotherapy strategies are under investigation for the treatment of earlier stages of disease or in other gynecologic cancers, such as ovarian cancer and rare gynecologic tumors. While the integration of ICIs into the standard of care has improved outcomes for patients, their use requires a nuanced understanding of biomarker testing, treatment selection, patient selection, response evaluation and surveillance, and patient quality of life considerations, among other topics. To address this need for guidance, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline. The Expert Panel drew on the published literature as well as their own clinical experience to develop evidence- and consensus-based recommendations to provide guidance to cancer care professionals treating patients with gynecologic cancer., Competing Interests: Competing interests: SFA – Contracted Research: Astra Zeneca. JB – Contracted Research: (institutional financial interests for conducted research) Eli Lilly, Novartis, Roche, Samsung Bioepis co. Ltd, Sun Pharma, Paxman Coolers. MOB – Consulting Fees: Bristol-Myers Squibb, EMD Serono, GSK, Immunocore, Immunovaccine, Merck & Co., Novartis, Sanofi-Genzyme, Turnstone Biologics, Sun Pharma; Contracted Research: Merck, Takara Bio. TJC – Consulting Fees: Agenus, Xencor; Ownership Interest less than 5%: Agenus, Xencor. MLD – Fees for non-CE services: PER; Contracted Research: Pfizer, EMD Serono, Bavarian Nordisk, Precigen, Epithany, Veanna; Other: Editor-in-Chief, JAMA Oncology; Other Details: Compensation by JAMA. LD – Consulting: Pfizer. LAE – Consulting Fees: Genentech, F Hoffman La Roche, Chugai, GPCR, Gilead, Immune Onc, Immutep, Shionogi, Mersana; Consulting (no fees): Immutep; Contracted Research: Abbvie, Astrazeneca, Bolt Therapeutics, Bristol Myers Squibb, Compugen, Corvus, CytomX, EMD Serono, Genentech, F Hoffman La Roche, Immune Onc, Maxcyte, Merck, Next Cure, Silverback, Takeda, Tempest; Other: HeritX Incorporated, NSABP Foundation, Translational Breast Cancer Research Consortium, Breast Cancer Research Foundation, National Cancer Institute, Department of Defense, Johns Hopkins University, University of California San Francisco, Cornell University, Dana Farber Cancer Institute, Stand Up to Cancer (these are grants from non-industry entities). CFF – Consulting Fees: Bristol-Myers Squibb, Arch Oncology, Seagen, Aptitude Health, OncLive, Aadi Biosciences/GOG Partners; Contracted Research: Genentech/Roche, Astra Zeneca, Bristol Meyers Squibb, Merck, Daiichi; Other: Merck, Genentech; Other Details: Scientific Advisory Board member (compensation waived). MEG – Consulting Fees: SeaGen (Tucatinib). MAG – Researcher: Fate Therapeutics, HCW Biologics; Consultant Advisor Speaker: Merck; NPI: 1265466809. AAJ – Consulting Fees: Nuprobe, Avenge Bio, BMS, Agenus, Instil Bio, GLG, Guidepoint, Macrogenics, Immune-Onc, Alkermes, EMD-Serono, Neo TILs, Genentech-Roche; Contracted Research: Iovance, AstraZeneca, BMS, Merck, Eli Lilly, Xencor, Immatics, Pfizer; Ownership Interest less than 5%: Avenge Bio. JBL – Contracted Research: Merck, Sanofi, AstraZeneca, Laekna, Sumitomo Dainippon Pharma Oncology, Harpoon Therapeutics, Precigen, Forty Seven. HM – Contracted Research: Puma Biotechnology. KO – Salary: The University of Chicago; IP Rights: PCT/US2014025673 “compositions and methods for use of recombinant T cell receptors for direct recognition of tumor antigen, PCT/US2014025456“ enhancement of vaccines; Consulting Fees: GOG Foundation/Celsion, GSK, Dailchi-Sanyo; Contracted Research: Astra Zeneca research funding (grant), Tessaro Pharma research funding (grant). EZ – NPI: 1598921181. SAD, KCK, AM, VSJ – Nothing to disclose. SITC Staff – EG, AK, NL, SMW – Nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Eribulin a microtubule targeting agent and analog of Halichondrin B, a natural product isolated from marine sponge H. okadai, has proven clinical efficacy in metastatic pretreated breast cancer and liposarcoma. We conducted a 2-stage Phase II study of eribulin in patients with advanced/recurrent cervical cancer to examine its clinical activity and evaluate biomarkers for predictors of response., Methods: Women with advanced/recurrent cervical cancer after ≤1 prior chemotherapy regimen, measurable disease and ECOG performance status ≤2 were treated with eribulin (1.4 mg/m 2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival (PFS6); secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS). Exploratory endpoints were associations of biomarkers with clinical activity. Immunohistochemistry was performed on archival tumor samples. Overexpression was defined when both intensity and distribution scores were ≥ 2., Results: 32 patients enrolled from 11/2012-5/2017. 29/32 patients had prior chemotherapy with cisplatin/paclitaxel/bevacizumab (n = 12) or cisplatin/gemcitabine (n = 12) as the most common regimens. 14 patients received prior paclitaxel. 1 (3%) had a complete response, 5 (16%) had a partial response and 13 (41%) had stable disease for ORR of 19% (95% CI 8, 37). Those who are paclitaxel naïve experienced the greatest benefit with a 29% ORR (95% CI 12, 54). Patients who received prior paclitaxel responded less favorably than those who did not (p = .002) and had a shorter PFS and OS. Grade 3/4 adverse events occurring in >10% of patients were anemia (n = 12, 38%), neutropenia (n = 7, 22%) and leukopenia (n = 6, 19%). Analysis of correlative predictors of response revealed that patients who did not overexpress βII and BAX were significantly more likely to respond to e`ribulin. PFS was significantly shorter in patients with βII and BAX overexpression, OS was significantly shorter in those with βIII and BAX overexpression. These associations remained after multivariate analysis., Conclusions: Eribulin shows modest activity in patients with recurrent/advanced cervical cancer with a favorable toxicity profile. Prior paclitaxel exposure is associated with decreased eribulin response. βII, βIII tubulin subtypes and BAX are predictors of response and survival. Eribulin may be an option for women with paclitaxel-naïve recurrent/advanced cervical cancer., Competing Interests: Declaration of Competing Interest Dr. Lin reports having financial interests in Genentech-Roche. Dr. Louie reports having received grants and research funding from the National Cancer Institute and the United States Department of Defense. Dr. A. Garcia reports participation in the Advisory Board for Biotheranostics Inc. Dr. Roman reports consulting for Cardiff Oncology, Nutcracker Therapeutics and AXDEV as well as participation in the Steering Committee for the Global Coalition of Adaptive Research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: A neural network method was employed to establish a dose prediction model for organs at risk (OAR) in patients with cervical cancer receiving brachytherapy using needle insertion., Methods: A total of 218 CT-based needle-insertion brachytherapy fraction plans for loco-regionally advanced cervical cancer treatment were analyzed in 59 patients. The sub-organ of OAR was automatically generated by self-written MATLAB, and the volume of the sub-organ was read. Correlations between D2cm 3 of each OAR and volume of each sub-organ-as well as high-risk clinical target volume for bladder, rectum, and sigmoid colon-were analyzed. We then established a neural network predictive model of D2cm 3 of OAR using the matrix laboratory neural net. Of these plans, 70% were selected as the training set, 15% as the validation set, and 15% as the test set. The regression R value and mean squared error were subsequently used to evaluate the predictive model., Results: The D2cm 3 /D90 of each OAR was related to volume of each respective sub-organ. The R values for bladder, rectum, and sigmoid colon in the training set for the predictive model were 0.80513, 0.93421, and 0.95978, respectively. The ∆D2cm 3 /D90 for bladder, rectum, and sigmoid colon in all sets was 0.052 ± 0.044, 0.040 ± 0.032, and 0.041 ± 0.037, respectively. The MSE for bladder, rectum, and sigmoid colon in the training set for the predictive model was 4.779 × 10 -3 , 1.967 × 10 -3 and 1.574 × 10 -3 , respectively., Conclusion: The neural network method based on a dose-prediction model of OAR in brachytherapy using needle insertion was simple and reliable. In addition, it only addressed volumes of sub-organs to predict the dose of OAR, which we believe is worthy of further promotion and application., (© 2023. The Author(s).)

Purpose: This study aimed to estimate the fitting parameters of sigmoidal dose-response (SDR) curve of radiation-induced acute rectal mucositis in pelvic cancer patients treated with Intensity Modulated Radiation Therapy (IMRT) for the calculation of normal tissue complication probability (NTCP)., Materials and Methods: Thirty cervical cancer patients were enrolled to model the SDR curve for rectal mucositis. The patients were evaluated weekly for acute radiation-induced (ARI) rectal mucositis toxicity and their scoring was performed as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The radiobiological parameters, namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of cervical cancer patients., Results: ARI toxicity for rectal mucosa in carcinoma of cervical cancer patients was calculated for the endpoint rectal mucositis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 rectal mucositis were found to be 0.328, 0.047, 25.44 ± 1.21 (confidence interval [CI]: 95%), and 8.36 and 0.13, 0.07, 38.06 ± 2.94 (CI: 95%), and 5.15, respectively., Conclusion: This study presents the fitting parameters for NTCP calculation of Grade 1 and Grade 2 ARI rectal toxicity for the endpoint of rectal mucositis. The provided nomograms of volume versus complication and dose versus complication for different grades of rectal mucositis help radiation oncologists to decide the limiting dose to reduce the acute toxicities., Competing Interests: None

Background: Bevacizumab is a monoclonal antibody drug targeting Vascular Endothelial Growth Factor (VEGF), which binds to VEGF receptors to inhibit vascular endothelial cell proliferation and angiogenesis, thus inhibiting tumorigenesis. Pembrolizumab is a monoclonal antibody that can bind to the programmed death-1 (PD-1) receptor, which can block the binding of the PD-1 receptor to its ligands PD-L1 and PD-L2, and release PD-1 pathway-mediated suppression of immune responses. By blocking the activity of PD-1, the purpose of inhibiting tumor growth is achieved., Case Presentation: We report a severe hematuria of bevacizumab plus pembrolizumab, in a 58-year-old woman with metastatic cervical cancer. After three cycles every three weeks of consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab) and following three cycles consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab, pembrolizumab), the patient presented a worsening state. Manifested as massive gross hematuria with blood clots. After stopping chemotherapy, cefoxitin, tranexamic acid and hemocoagulase atrox therapy was administered resulting in rapid clinical improvement. The patient was a cervical cancer with bladder metastasis that increases the risk of development of hematuria. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival influences on endothelial cells, weakens their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, the development of hematuria may result from the anti-VEGF effect of bevacizumab. In addition, pembrolizumab may also cause bleeding, and the mechanism of bleeding caused by pembrolizumab is currently unclear, which may be related to immune mediation., Conclusion: To our knowledge, this is the first case reporting on the development of severe hematuria during bevacizumab plus pembrolizumab treatment, which should alert the clinicians in case of bleeding adverse events onset in older patients under bevacizumab plus pembrolizumab therapy., (© 2023. The Author(s).)

Objective: Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship., Methods: Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models., Results: We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53-1.88] and 2.11 (95% CI, 1.85-2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02-1.24) and 1.29 (95% CI, 1.15-1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34-2.20 for invasive CC and RR = 2.13; 95% CI, 1.86-2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting., Conclusion: This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A semiconductor rectal probe was used to compare planned and measured rectal doses during Co-60 high dose rate (HDR) CT-based intracavitary brachytherapy applications (ICBT) of cervical cancer., Materials and Methods: A total of 22 HDR brachytherapy applications were included from 11 patients who were first treated with EBRT to the whole pelvis with a total prescribed dose of 50 Gy in 25 fractions. During each application, a PTW 9112 probe rectal probe having a series of five semiconductor diodes (R1 to R5) was inserted into the patient's rectum and a CT-based HDR ICBT application with a prescribed dose per fraction of 7 or 7.5 Gy to HRCTV was performed. Measurements were carried in water phantom using PTW rectal and universal adaptor plugs. Doses measured in phantom and with patients were compared to those calculated by the treatment planning system., Results: The mean percentage dose difference ΔD (%) between calculated and measured values from phantom study were -5.29%, 1.89%, -2.72%, -4.76, and 0.72% for R1, R2, R3, R4, and R3 diodes, respectively and the overall mean ΔD (%) value with standard deviation (SD) was -2.03%±9.6%. From the patient study, a ΔD (%) that ranged from -19.5% to 24.0%, which corresponded to dose disparities between -0.77 Gy and 0.66 Gy. The median ΔD (%) ranged from 0.4% to 1.3%, or -0.03 to 0.05 Gy, respectively. ΔD (%) values exceeded 10% in approximately 26.4% of measurements (29 out of 110 in 22 applications). The location of Rmax in computed and measured values differs in 5 of 22 applications might be due to possible displacement of rectal probe between simulation and treatment., Conclusion: Despite the likely geometrical shift of measuring detectors between insertion and treatment, in-vivo dosimetry is feasible and can be used to estimate the dose to the rectum during HDR ICBT.

Background: While health risk behaviours are likely to co-occur, there is dearth of studies exploring the clustering of cervical cancer and HPV infection risk factors among adolescents. This study aimed to determine: 1) the prevalence of modifiable risk factors for cervical cancer and HPV infection, 2) the clustering of modifiable risk factors for cervical cancer and HPV infection, and 3) factors associated with the identified clusters., Methods: Female students (aged 16-24 years, N = 2400) recruited from 17 randomly selected senior high schools in the Ashanti Region, Ghana completed a questionnaire assessing modifiable risk factors for cervical cancer and HPV infection including sexual experience, early sexual intercourse (< 18 years), unprotected sex, smoking, sexually transmitted infections (STIs); multiple sexual partners (MSP) and smoking. Latent class analysis explored separate classes of students according to their risk factor profiles for cervical cancer and HPV infection. Latent class regression analysis explored factors associated with latent class memberships., Results: Approximately one in three students (34%, 95%CI: 32%-36%) reported exposure to at least one risk factor. Two separate classes emerged: high-risk and low-risk (cervical cancer: 24% and 76% of students, respectively; HPV infection: 26% and 74% of students, respectively). Compared to participants in the low-risk classes i) the cervical cancer high-risk class were more likely to report exposure to oral contraceptives; early sexual intercourse (< 18 years); STIs; MSP and smoking; and ii) the HPV infection high risk class were more likely to report exposure to sexual intercourse; unprotected sex and MSP. Participants with higher risk factor knowledge had significantly higher odds of belonging to cervical cancer and HPV infection high-risk classes. Participants with greater perceived susceptibility to cervical cancer and HPV infection were more likely to belong to the high-risk HPV infection class. Sociodemographic characteristics and greater perceived seriousness about cervical cancer and HPV infection had significantly lower odds of belonging to both high-risk classes., Conclusions: The co-occurrence of cervical cancer and HPV infection risk factors suggests that a single school-based multi-component risk reduction intervention could concurrently target multiple risk behaviours. However, students in the high risk class may benefit from more complex risk reduction interventions., (© 2023. The Author(s).)

Introduction: Breast and cervical cancers represent two important causes of cancer-associated deaths in females. Uptake in prevention towards these cancers remains low in the United Arab Emirates., Objectives: This study aimed to understand the knowledge, attitudes and practices of females residing in the Al Ain city, UAE, towards cervical and breast cancer prevention., Methods: This cross-sectional survey was conducted with 300 women, aged 30 years and above. The primary outcome measure was cervical and breast cancer prevention knowledge. The knowledge was queried through a number of items, with the resulting aggregate scores categorized into good and low knowledge. Chi-square test was conducted to investigate the association between prevention knowledge and sociodemographic factors. Additional outcomes included attitude towards and uptake of cervical and breast cancer screening., Results: Of the participants surveyed, 36.7% had good knowledge on breast cancer prevention, while 5.3% on cervical cancer prevention. Although the majority of the participants believed that prevention methods could save lives, they reported negative attitudes, considering screening unnecessary and painful. The self-reported screening uptake was 23% and 31.3% for mammography and Pap smear, respectively., Conclusions: The study reported that the knowledge and uptake of women was low for both breast and cervical cancer prevention. Targeted campaigns not only to increase knowledge but also to resolve misconceptions to change negative attitudes may lead to an increase in uptake., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT)., Design: A retrospective cohort study., Setting: Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China., Population: Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited., Methods: This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6 and 5 Gy per fraction for five fractions, respectively., Results: Mean HR-CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen., Conclusions: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour., (© 2022 John Wiley & Sons Ltd.)

Diverse dietary constituents, encompassing both macro- and micronutrient intakes, have established connections with various cancers, though their specific roles in cervical cancer remain unclear. This study explores dietary intake correlations among women aged 30 yrs and above diagnosed with cervical cancer ( n  = 215), contrasted with women without ( n  = 860). These populations were selected from the 1999-2018 cycle of the National Health and Nutrition Examination Survey. The research implemented the univariate analysis and the least absolute shrinkage and selection operator (LASSO) regression to estimate the association of 29 variables with cervical cancer, subsequently identifying the most pertinent variables linked to cervical cancer. Six covariates emerged as significantly associated with cervical cancer in univariate analyses (age, race, fiber, magnesium, caffeine, vitamin C) ( p  < 0.05). In LASSO regression, with the escalating penalty factor (λ), it was discerned that specific covariates, including age, race, fiber, and Vitamin C, consistently remained in the model. Univariate analysis and logistic LASSO regression findings suggested that diets deficient in fiber and vitamin C were related to cervical cancer.

Introduction: Carcinoma cervix (CACX) is a common gynecological malignancy and locally advanced CACX is treated with radical chemoradiation, followed by brachytherapy boost. The appropriate selection of tandem angle is needed for optimal dose distribution and to avoid perforations. The aim of our study was to assess the appropriate tandem angle selection based on uterine angle measured on external beam radiotherapy (EBRT) planning imaging and to assess the need for repeat imaging and image-guided placement of tandem during intracavitary brachytherapy based on risk factors., Methods: This is a single-institute, two-arm retrospective, observational study to improve quality of brachytherapy in CACX patients (n = 206), with uterine perforation/suboptimal tandem placement (UPSTP) in arm A and optimally inserted in arm B. The uterine angle was measured from EBRT planning CT-scan and correlated with brachytherapy planning CT-scan and other risk factors in relation to UPSTP., Results: The uterine angle was 30 o (±30 o ) and 17 o (±21 o ) on EBRT and brachytherapy planning CT-scan, respectively, and significantly was different (P < 0.00001). There were 40 (19%) perforations and 52 (25%) suboptimal tandem placements (uterine subserosal/muscle insertion). The most common site of perforation was posterior then anterior and central. There was higher chance of UPSTP with hydrometra, huge uterus with tumor (HMHU) or retroverted uterus (RU), P = 0.006 and 0.14, respectively. The persistence of HMHU or RU during brachytherapy leads to higher UPSTP, P = 0.000023 and 0.18, respectively., Conclusion: Uterine angle measurement on EBRT planning CT-scan varies significantly when measured on brachytherapy planning CT-scan and cannot be used for selection of tandem. Reimaging before brachytherapy should be considered in advanced CACX with HMHU or RU at presentation and image-guided placement of tandem should be used if HMHU or RU persists during brachytherapy.

PD-1 (Programmed cell death-1) is a receptor that inhibits the activation of T cells and is an important target for cancer immunotherapy. PD-1 expression stays high on antigen-specific T cells that have been stimulated for a long time, making them less responsive to stimuli. Consequently, there has been a recent surge in the number of researchers focusing on how the PD-1 axis delivers inhibitory signals to uncover new therapeutic targets. As an inhibitory signaling mechanism, the PD-1 axis controls immunological responses. Blocking the PD-1 axis has been shown to have long-lasting effects on various cancers, demonstrating the crucial role of PD-1 in blocking anti-tumor immunity. Despite this role, most patients do not respond to PD-1 monotherapy, and some have experienced adverse events. Many challenges remain regarding the PD-1 signaling axis to be addressed. In this review, we outline the most recent research and prospects of PD-1 signal inhibitors to enhance cervical cancer therapy., Competing Interests: Conflicts of interest The authors have declared that no competing interest exists., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: External beam radiotherapy remains the primary treatment modality in cervical cancer. Nowadays Intensity Modulated Radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are increasingly being used to reduce normal tissue toxicity. The drawback of conventional  VMAT is that a considerable volume of pelvic bone marrow receives a low dose., Aim: We analyzed whether there was a way to reduce the volume of the low dose regions of bone marrow, and assessed the potential benefit of conventional-4Arc (C-4Arc VMAT), and Modified-4Arc (M-4Arc VMAT) over the conventional 2 ARC VMAT., Materials and Methods: Twelve clinically proven locally advanced cervical cancer patients treated with concurrent chemo-radiotherapy by Conventional VMAT (RapidArc) in dual rotation mode (C-2Arc VMAT) were selected for this study.C-4Arc VMAT and M-4Arc VMAT dose plans were generated for these twelve patients and these three different types of plans were evaluated for the quality and compared dosimetrically., Results: M-4Arc VMAT designs exhibited a greater bone marrow sparing when compared with conventional VMATs with respect to volume receiving 5Gy to 35Gy without compromising PTV dose coverage. M-4Arc VMAT plans, the bone marrow volume receiving 30 Gy (V30Gy),40Gy (V40Gy), and mean doses were lower than the C- 4 Arc plan and a similar result was observed for V50(Gy) also when comparing with the standard 2 Arc plan. In modified VMAT plans, the rectum and bladder dose volumes were lower than standard VMAT. Similarly, the bowel bag V35(Gy), V40(Gy), V50(Gy), mean doses. The right and left femoral head doses were reduced significantly when compared to conventional VMAT plans., Conclusion: The M-4Arc VMAT plans are better than the C-2Arc and C-4Arc VMAT plans for reducing the dose to bone marrow by limiting the MLC field width travel.

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery., Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks)., Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity ( p  = .014) was higher and a history of preterm delivery ( p  = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group ( p  = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p  = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p  < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p  = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p  = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p  = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women., Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Background: Gynecological cancers, including cervical cancer, ovarian cancer and endometrial cancer are leading causes of cancer-related death in women worldwide. Diet plays an important role in cancer development, which is widely accepted. However, the associations between dietary intakes and gynecological cancers remain unclear. Methods: A total of 12,437 women aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007−2016, were included in this study. The relationships between 30 dietary factors (4 macronutrients, 15 vitamins, 9 minerals, caffeine and alcohol) and gynecological cancers were assessed. Results: We observed negative correlations of intakes of phosphorus (odds ratio (OR), 95% confidence interval (CI); 0.998 (0.996, 0.999), p = 0.002) with cervical cancer, and intakes of vitamin B12 (0.812 (0.714, 0.925), p = 0.002), phosphorus (0.997 (0.996, 0.999), p < 0.001) and alcohol (0.971 (0.950, 0.992), p = 0.009) with endometrial cancer. The data showed positive associations of intake of caffeine (1.002 (1.001, 1.003), p = 0.003) with cervical cancer, and intake of copper (2.754 (1.313, 5.778), p = 0.009) with endometrial cancer. In addition, we found potential negative correlations between intake of vitamin B1 (p = 0.025) and cervical cancer; zinc (p = 0.048) and ovarian cancer; and potassium (p = 0.032) and endometrial cancer. Potential positive associations were found between intake of calcium and cervical cancer (p = 0.026) and endometrial cancer (p = 0.034), and between sodium (p = 0.042) and endometrial cancer. Intakes of protein, total sugars, total fat, cholesterol, vitamin A, alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, vitamin B2, niacin, vitamin B6, food folate, vitamin C, vitamin D, vitamin E, vitamin K, magnesium, iron and selenium showed no relationship with gynecological cancers (p > 0.05). Conclusions: Specific dietary factors were associated with gynecological cancers. More epidemiological studies are needed to validate our results.

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m 2  + cisplatin 50 mg/m 2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD-L1 combined positive score (CPS) ≥1, all-comers, and PD-L1 CPS ≥10. Fifty-seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD-L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16-0.77]), all-comers (n = 57; 0.45 [0.22-0.90]), and patients with PD-L1 CPS ≥10 (n = 25; 0.36 [0.12-1.07]). HRs (95% CI) for OS were 0.38 (0.14-1.01), 0.41 (0.17-1.00), and 0.37 (0.10-1.30), respectively. Incidence of grade 3-5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE-826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)