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The prevalence of different HPV types, especially HPV16 and 18 in cervical cancer in patients diagnosed 2019–2023 in Stockholm was compared to corresponding data from 2003–2008 before the introduction of HPV vaccination in Sweden. Cervical cancer samples from 125 patients diagnosed 2019–2023 in Stockholm were analysed for 27 HPV types by multiplex assay and the HPV type prevalence data was compared to data obtained in 154 cervical samples from 2003–2008. Patient median age was higher 2019–2023 compared to 2003–2008 (55-years vs. 42-years, p = 0.046). Overall HPV prevalence was 93.6%, HPV16 and 18 accounted for 62.2% of all squamous cell carcinoma cases (SCC) and 63.6% of all adenocarcinoma cases (ADC) vs. 92.9%, 69.7% and 88.6% respectively 2003–2008. The joint prevalence of HPV16 and 18 in SCC and ADC tended to be slightly lower in 2019–2023 as compared to 2003–2008, but the difference was not statistically significant. [ABSTRACT FROM AUTHOR]

Cancer treatment during reproductive ages may negatively impact fertility and there is a need of firm knowledge about the prevalence and predictors of fertility-related distress. The aim was to examine fertility-related distress in a population-based sample of young women and men recently treated for cancer and to identify predictors for this outcome. This nationwide cohort study included 1010 individuals (694 women and 316 men), mean age 34.5 ± 4.9 and 32.1 ± 5.5, respectively, diagnosed with breast, cervical, ovarian, testicular cancers, brain tumors or lymphoma at ages 18–39 in Sweden. Participants completed a survey 1.5-year post-diagnosis to assess fertility-related distress (RCAC), emotional distress (HADS) and self-efficacy, as well as sociodemographic and clinical factors and fertility preservation. Logistic regression was used to examine associations between explanatory factors and high fertility-related distress (RCAC subscale mean >4). Many participants (69% of women and 47% of men) had previous children and about half reported a wish for future children. High fertility-related distress was more prevalent among women (54%) than men (27%), and women were more likely than men to report distress concerning all but one RCAC dimension after adjustment for sociodemographic factors. Use of fertility preservation was unevenly distributed (15% of women and 71% of men) and was not associated with decreased fertility-related distress. In multivariable logistic regression models, a wish for future children, being single, not having previous children, symptoms of anxiety and low self-efficacy regarding one's ability to handle threats of infertility were associated with high fertility-related distress. This nationwide study found a high prevalence of fertility-related distress in young women and men recently treated for cancer and identified sociodemographic and psychological predictors. Fertility preservation was not found to act as a buffer against fertility-related distress, indicating the continuous need to identify strategies to alleviate fertility distress following cancer. [ABSTRACT FROM AUTHOR]

Tumor cells release fragments of their DNA into the circulation, so called cell‐free tumor DNA (ctDNA), allowing for analysis of tumor DNA in a simple blood test, that is, liquid biopsy. Cervical cancer is one of the most common malignancies among women worldwide and high‐risk human papillomavirus (HR‐HPV) is the cause of the majority of cases. HR‐HPV integrates into the host genome and is often present in multiple copies per cell and should thus also be released as ctDNA. Such ctHPV DNA is therefore a possible biomarker in cervical cancer. In this review, we first give a background on ctDNA in general and then a comprehensive review of studies on ctHPV DNA in cervical cancer and pre‐malignant lesions that may develop in cervical cancer. Furthermore, studies on ctHPV DNA in other HPV related malignancies (eg, head‐and‐neck and anogenital cancers) are briefly reviewed. We conclude that detection of ctHPV DNA in plasma from patients with cervical cancer is feasible, although optimized protocols and ultra‐sensitive techniques are required for sufficient sensitivity. Results from retrospective studies in both cervical cancer and other HPV‐related malignancies suggests that ctHPV DNA is a promising prognostic biomarker, for example, for detecting relapses early. This paves the way for larger, preferably prospective studies investigating the clinical value of ctHPV DNA as a biomarker in cervical cancer. However, there are conflicting results whether ctHPV DNA can be found in blood from patients with pre‐malignant lesions and further studies are needed to fully elucidate this question. [ABSTRACT FROM AUTHOR]

Background: Sexual dysfunction is common following a cancer diagnosis in young adulthood (18–39 years) and problems related to sex life are ranked among the core concerns in this age group. Yet, few studies have investigated to what extent adults younger than 40, receive information from healthcare providers about the potential impact of cancer and its treatment on their sex life. Methods: A population‐based cross‐sectional survey study was conducted with 1010 young adults 1.5 years after being diagnosed with cancer (response rate 67%). Patients with breast, cervical, ovarian and testicular cancer, lymphoma, and brain tumors were identified in national quality registries. Sociodemographic and clinical factors associated with receiving information were examined using multivariable binary logistic regression. Results: Men to a higher extent than women reported having received information about potential cancer‐related impact on their sex life (68% vs. 54%, p < 0.001). Receipt of information varied across diagnoses; in separate regression models, using lymphoma as reference, both women and men with brain tumors were less likely to receive information (women: OR 0.10, CI = 0.03–0.30; men: OR 0.37, CI = 0.16–0.85). More intensive treatment was associated with higher odds of receiving information in both women (OR 1.89; CI = 1.28–2.79) and men (OR 2.08; CI = 1.09–3.94). None of the sociodemographic factors were associated with receipt of information. Conclusions: To improve sexual health communication to young adults with cancer, we recommend diagnosis‐specific routines that clarify when in the disease trajectory to discuss these issues with patients and what to address in these conversations. [ABSTRACT FROM AUTHOR]

Self-reported sex problems among women diagnosed with reproductive and nonreproductive cancers before the age of 40 are not fully understood. This study aimed to determine sexual dysfunction in young women following a cancer diagnosis in relation to women of the general population. Furthermore, to identify factors associated with sexual dysfunction in women diagnosed with cancer. A population-based cross-sectional study with 694 young women was conducted 1.5 years after being diagnosed with cancer (response rate 72%). Potential participants were identified in national quality registries covering breast and gynecological cancer, lymphoma and brain tumors. The women with cancer were compared to a group of women drawn from the general population (N = 493). Sexual activity and function were assessed with the PROMIS® SexFS. Logistic regression was used to assess differences between women with cancer and the comparison group, and to identify factors associated with sexual dysfunction. The majority of the women with cancer (83%) as well as the women from the comparison group (87%) reported having had sex the last month (partner sex and/or masturbation). More than 60% of the women with cancer (all diagnoses) reported sexual dysfunction in at least one of the measured domains. The women with cancer reported statistically significantly more problems than women of the comparison group across domains such as decreased interest in having sex, and vaginal and vulvar discomfort. Women with gynecological or breast cancer and those receiving more intense treatment were at particular high risk of sexual dysfunction (≥2 domains). Concurrent emotional distress and body image disturbance were associated with more dysfunction. The results underscore the need to routinely assess sexual health in clinical care and follow-up. Based on the results, development of interventions to support women to cope with cancer-related sexual dysfunction is recommended. [ABSTRACT FROM AUTHOR]

Introduction: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long‐term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. Material and Methods: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997–2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow‐up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow‐up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. Results: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow‐up time of 7.1 years (interquartile range 3.1–13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population‐based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03–0.53) after EA and 1.27 (95% CI 0.86–1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. Conclusions: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate. [ABSTRACT FROM AUTHOR]

Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08–1.66) followed by country of birth (OR 1.31, 95% CI 1.10–1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36–3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis. Surgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival. A prolonged wait time to surgery did not worsen prognosis. Delay in time to surgery was associated with sociodemographic factors. [ABSTRACT FROM AUTHOR]

Introduction: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. Material and methods: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I‐III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. Results: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. Conclusions: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI. [ABSTRACT FROM AUTHOR]

Infertility is a well-known sequela of cancer treatment. Despite guidelines recommending early discussions about risk of fertility impairment and fertility preservation options, not all patients of reproductive age receive such information. This study aimed to investigate young adult cancer patients' receipt of fertility-related information and use of fertility preservation, and to identify sociodemographic and clinical factors associated with receipt of information. A population-based cross-sectional survey study was conducted with 1010 young adults with cancer in Sweden (response rate 67%). The inclusion criteria were: a previous diagnosis of breast cancer, cervical cancer, ovarian cancer, brain tumor, lymphoma or testicular cancer between 2016 and 2017, at an age between 18 and 39 years. Data were analyzed using logistic regression models. A majority of men (81%) and women (78%) reported having received information about the potential impact of cancer/treatment on their fertility. A higher percentage of men than women reported being informed about fertility preservation (84% men vs. 40% women, p <.001) and using gamete or gonadal cryopreservation (71% men vs. 15% women, p <.001). Patients with brain tumors and patients without a pretreatment desire for children were less likely to report being informed about potential impact on their fertility and about fertility preservation. In addition, being born outside Sweden was negatively associated with reported receipt of information about impact of cancer treatment on fertility. Among women, older age (>35 years), non-heterosexuality and being a parent were additional factors negatively associated with reported receipt of information about fertility preservation. There is room for improvement in the equal provision of information about fertility issues to young adult cancer patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010–2017 with FIGO stages I–III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69–8.07, p <.001) followed by deep myometrial invasion (RR = 1.64, CI 1.13–2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03–29.10,) and non-diploidy (EMR = 3.23, CI 1.25–8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05–5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important. [ABSTRACT FROM AUTHOR]

Background:The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer. Method:This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009–2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations. Results:Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99,p = .001) or other/multiple distant sites (HR 2.67,p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245). Conclusion:Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients. [ABSTRACT FROM AUTHOR]

Aim:The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC). Method:A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson’s correlation coefficient and Cohen´s kappa coefficient. Results:The completeness was 95%. The timeliness was 88–91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson’s correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70–81%; kappa 0.49) and type of primary treatment 90% (95% CI 87–94%; kappa 0.85) in OC and in EC 88% (95% CI 84–93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68–80%; kappa 0.69) and 87% (95% CI 82–91%; kappa 0.79), respectively. Conclusions:The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results. [ABSTRACT FROM AUTHOR]

Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients. Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses. Results: The majority of PVC patients (72%) had >50% LRIG1- and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival. Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified. [ABSTRACT FROM AUTHOR]

Background: As the choice of treatment in patients with cervical carcinoma depends on cancer stage at diagnosis, accurate staging is essential. Purpose: To compare three different combinations of magnetic resonance (MR) sequences for preoperative staging. Material and Methods: Fifty-seven consecutive patients with biopsy proven cervical carcinoma underwent MR imaging (MRI) staging followed by primary surgical treatment. Thirty-two of 57 patients had had a cone biopsy prior to MRI. Three MR pulse sequence combinations were retrospectively reviewed by two experienced radiologists. The first imaging protocol consisted of pre-contrast sagittal and transverse images (protocol A), the second protocol included additionally oblique high-resolution T2-weighted (T2W) MR images of the cervix (protocol A+B), and the third included also contrast-enhanced sequences (protocol A+B+C). The imaging findings in the three steps (A, A+B, A+B+C) were recorded. The TNM stage was used for comparison between preoperative imaging and histopathology. Histopathology, together with surgical findings, served as gold standard. Results: In 4/57 (7%) patients, the MR assessment of tumor stage (mrT) was altered when oblique sequences were added to the standard two plane imaging protocol (A+B). The mrT stage was altered in 1/57 (2%) patient when contrast-enhanced sequences were added to standard and oblique sequences (protocol A+B+C). The correlation between visible tumor on MRI and presence of tumor in the resected specimen did not change by adding oblique or contrast-enhanced images. Conclusion: It is not necessary to perform oblique and contrast-enhanced sequences in small cervical carcinomas, i.e. without parametrial invasion. To avoid erroneous interpretation, information on previous cone biopsy is essential. [ABSTRACT FROM AUTHOR]

Since the introduction of screening programs for cervical cancer ( CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma ( CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics ( FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma ( SCC) cases and a sixfold increase in the proportion of adenocarcinoma ( AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits). [ABSTRACT FROM AUTHOR]

This study aimed to analyze the prognostic value of DNA content and biological markers for cell cycle regulation and invasion in primary carcinoma of the vagina (PCV).Seventy-two consecutive patients with PCV, categorized as short-term (2 years) and long-term (≥8 years) survivors, were evaluated for DNA content by image cytometry, and for expression of p53, p21, cyclin A, Ki67, E-cadherin, and laminin-5γ2 chain by immunohistochemistry. The relationship between these biological markers and histopathological and clinical parameters was assessed.All PCV showed aneuploid DNA content. Most of the PCV patients showed no overexpression of p53 and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E-cadherin was found in 94% (68/72) of PCV patients, and all patients showed immunopositivity for the laminin-5γ2 chain. Tumors with a vaginal longitudinal location in the lower third or in the entire vagina more often had overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression of E-cadherin (P = 0.038), than tumors confined only to the upper third. Overexpression of p53 was significantly associated with short-term survival in the univariate analysis, but not in the multivariate analysis adjusted for age at diagnosis and tumor size.The expression level of some markers was related to tumor location, which might be indicative of different genesis. Overexpression of p53 was associated with short-term survival, but the only independent predictors of survival were age at diagnosis and tumor size. [ABSTRACT FROM AUTHOR]

P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. The proteins interact with the 5S rRNA with nearly identical binding characteristics. We have shown that this interaction is achieved mainly through the LoopA region of the RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now provide evidence to show that these factors form a novel pre-ribosomal particle through interactions with both 5S rRNA and the L5 ribosomal protein. Further in silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it and aiding in the early steps of ribosome biogenesis. [ABSTRACT FROM AUTHOR]

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC. [ABSTRACT FROM AUTHOR]

ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) evaluated pembro + CCRT in patients (pts) with high-risk LACC. Pts with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB with node-positive disease or stage III‒IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or placebo (pbo) Q3W + CCRT then 15 cycles of pembro 400 mg or pbo Q6W. CCRT was 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 QW + EBRT then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator or histopathologic confirmation and OS. 1060 pts were randomized to pembro + CCRT (n = 529) or pbo + CCRT (n = 531). At IA1 (data cutoff: Jan 9, 2023), median follow-up was 17.9 mo. Pts received a median of 11 cycles of pembro or pbo and 5 cycles of cisplatin in both arms. Most pts completed radiation treatment (pembro + CCRT, 97.9%; pbo + CCRT, 98.3%); overall median treatment duration was 52 d in both arms. Table 1 summarizes the CCRT treatment. Pembro + CCRT improved PFS vs pbo + CCRT (HR 0.70 [95% CI 0.55‒0.89]; P = 0.0020). Median PFS was not reached in either arm. PFS benefit was generally consistent across prespecified subgroups. With only 103 events (42.9% maturity), pembro + CCRT had a favorable trend in OS (HR 0.73 [95% CI 0.49‒1.07]). Treatment-related AEs (TRAEs) were less common in the pembro monotherapy phase (72.7%) vs pembro + CCRT combination therapy phase (94.5%); results in the pbo arm were 60.0% vs 95.7%. Safety profiles were consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS vs pbo + CCRT in pts with high-risk LACC. Pembro + CCRT had manageable safety, with most TRAEs occurring during the combination phase of therapy. Pembro + CCRT has potential as a new standard of care for this high-risk population. [ABSTRACT FROM AUTHOR]