Uterine Cervical Cancer Research Articles

Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer.

Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.

Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

AIM: This study aims to determine the relationship between the HPV genotype in uterine cervical cancer and the expression of HIF-1α due to tissue hypoxia and its impact on radiation response. METHODS: This study is an analytic and observational study with a cross-sectional design with the inclusion criteria in this study that was new cervical cancer Stage IIB, IIIA, IIIB, and IVA patients treated at the oncology polyclinic who had never undergone radiotherapy and would be treated with radiation. RESULTS: Sixty patients advanced cervical cancer aged 25 to &gt;45 years were involved patients. The majority had HPV genotype 16 infections. There was no significant relationship between treatment response and HPV genotype (HPV 16 genotype [p = 0.844], HPV 18 genotype [p = 0.161], other HPV genotypes [p = 0.108]), radiation response with HIF-1α expression (p = 0.503; OR 1.569 [0.417–5.899]), HIF1α expression with HPV genotype (HPV genotype 16 (p = 0.648; OR 1,357 [0.356–5.041]), HPV 18 genotype (p = 0.344; OR 1,458 [0.089–2.373]), and other HPV genotypes (p = 0.505; OR 1.667 [0.368–7.553]) as well as HIF-1α expression and HPV genotypes to radiation response (p &gt; 0.05). CONCLUSION: Cervical cancer with infection with HPV Genotype 18 tends to express HIF1α strongly and increased partial radiation response. Overall statistically, there was no significant association between infection with certain genotypes of HPV with radiation response or HIF-1α expression in tumor tissue with radiation response.

Disability-Adjusted Life Year (DALY) assessment and economic damage from premature death of cervical uterine and ovarian cancers in the Tomsk Region

Background. Disability-adjusted life year (DALY) is one of the well-known methods of comprehensive health assessment in the world. The method was developed by the World Bank and the World Health Organization. The DALY units and gross domestic product per capita are used for the assessment of the indirect economic damage from premature death of cancer.&#x0D; Aim. To estimate the number of years of life lost (DALY method) and economic losses due to death from cervical, uterine and ovarian cancers in the population of the Tomsk region.&#x0D; Materials and methods. The data of the Tomsk Region Federal State Statistics Service on the mortality of the population of the reporting form C51 Distribution of the dead by sex, age groups and causes of death, data on the sex and age distribution of the population, life expectancy, gross regional product per capita for 2018 of the Tomsk region were used.&#x0D; Results. In 2018, due to the death from gynecological cancer of the population of the Tomsk Region, 1616 DALY units were lost in absolute numbers. Of these, cervical cancer accounts for 44.3% (717 DALY units), uterine corpus cancer accounts for 24.8% (401 DALY units), ovarian cancer accounts for 30.8% (498 DALY units). At working age (1654 years), the absolute losses amounted to 694 DALYs. The economic damage to the Tomsk Region due to the mortality of the population from cancer of the cervix, uterine body and ovaries in 2018 amounted to 918.2 million rubles. Economic losses as a result of mortality from cancer of the cervix amounted to 407.4 million rubles, from cancer of the ovaries 283.0 million rubles, from cancer of the body of the uterus 227.8 million rubles. The economic damage from gynecological cancers in working age amounted to 394.3 million (42.9% of the total economic damage).&#x0D; Conclusion. Determining the socio-economic losses associated with mortality from malignant neoplasms of the female genital organs is necessary for the effective use of health care resources, which can be used to justify the need of the population for oncological care.

BRAIN METASTASIS FROM UTERINE CERVICAL CANCER

Uterine cervical cancer usually spreads by local extension and through the rich lymphatic network to the retroperitoneal lymph nodes. However, brain metastasis from primary cervical cancer is extremely rare. They are usually seen late in the clinical course and have poor prognosis. We present a52-year-old woman with squamous cell carcinoma of the cervix who developed brain and other multiple metastases after 8-month treatment of the primary disease. The patient showed up neurologic symptoms and received one session of brain radiation therapy and steroids, then she died one month later.

Treatment of HPV-Related Uterine Cervical Cancer with a Third-Generation Oncolytic Herpes Simplex Virus in Combination with an Immune Checkpoint Inhibitor.

Cervical cancer is one of the most common cancers in women. The development of new therapies with immune checkpoint inhibitors (ICIs) is being investigated for cervical cancer; however, their efficacy is not currently sufficient. Oncolytic virus therapy can increase tumor immunogenicity and enhance the antitumor effect of ICIs. In this report, the therapeutic potential of a triple-mutated oncolytic herpes virus (T-01) with an ICI for human papillomavirus (HPV)-related cervical cancer was evaluated using a bilateral syngeneic murine model. The efficacy of intratumoral (i.t.) administration with T-01 and subcutaneous (s.c.) administration of anti-programmed cell death ligand 1 (PD-L1) antibody (Ab) was equivalent to that of anti-PD-L1 Ab alone on the T-01-injected side. Moreover, combination therapy had no significant antitumor effect compared to monotherapy on the T-01-non-injected side. Combination therapy significantly increased the number of tumor specific T cells in the tumor. While T-01 could not be isolated from tumors receiving combination therapy, it could be isolated following T-01 monotherapy. Furthermore, T-01 had a cytotoxic effect on stimulated T cells. These results suggest that T-01 and anti-PD-L1 Ab partially counteract and therefore concomitant administration should be considered with caution.

CLEFMA induces intrinsic and extrinsic apoptotic pathways through ERK1/2 and p38 signalling in uterine cervical cancer cells.

Although concurrent chemoradiotherapy is the cornerstone of treatment for locally advanced or recurrent uterine cervical cancer, treatment fails at a high rate. Therefore, the development of novel targeting agents is critical. This study investigated the action of CLEFMA, a potent, synthetic curcumin derivative, on cervical cancer cells and its mechanism of action. We found that CLEFMA negatively regulated the viability of cervical cancer cells, involving induction of cell apoptosis. Cleaved caspase-3, cleaved poly(adenosine diphosphate-ribose) polymerase, cleaved caspase-8, and cleaved caspase-9 expression were increased by treatment with CLEFMA. After U0126 (ERK1/2 inhibitor) and SB203580 (p38 inhibitor) were applied as cotreatment with CLEFMA, the expression of cleaved caspase-8, -9, and -3 was reduced significantly. In conclusion, CLEFMA activates both extrinsic and intrinsic apoptotic pathways through ERK1/2 and p38 signal transduction in cervical cancer cells.

Phase Angle and Nutritional Status: The Impact on Survival and Health-Related Quality of Life in Locally Advanced Uterine Cervical Cancer.

The phase angle, an indicator of muscle mass status and membrane cell integrity, has been associated with low survival, poorer clinical outcomes, and worse quality of life among cancer patients, but information on women with uterine cervical cancer (UCCa) is scarce. In this prospective study, we used a bioelectrical impedance analyzer to obtain the PA of 65 women with UCCa. We compared the health-related quality of life and inflammatory and nutritional indicators between low PA and normal PA. The mean age was 52 ± 13. The low PA and normal PA groups differed in terms of the C-reactive protein (15.8 ± 19.6 versus 6.82 ± 5.02, p = 0.022), glucose (125.39 ± 88.19 versus 88.78 ± 23.08, p = 0.021), albumin (3.9 ± 0.39 versus 4.37 ± 0.30, p = 0.000), EORTC QLQ-C30 loss of appetite symptom scale score (33.33 (0.0-100.00) versus 0.0 (0.0-0.0), p = 0.005), and EORTC QLQ-CX24 menopausal symptoms scale score (0.0 (0.0-33.33) versus 0.0 (0.0-100.0), p = 0.03). The main finding of the present study is the interaction between PA and obesity as critical cofactors in the UCCa adeno and adenosquamous histologic variants, to a greater extent than cervical squamous cell carcinoma.

Treatment Tolerability and Toxicity of Postoperative Proton Beam Therapy for Gynecologic Malignancies: Results of the Prospective Phase 2 APROVE Trial

The APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women with uterine cervical or endometrial cancer. In this analysis, we report the primary study endpoint of safety and treatment tolerability as well as toxicity rates and progression-free survival (PFS). 25 patients were treated with postoperative proton beam therapy with a total dose of 45 to 50.4 Gy (RBE) in 5 to 6×1.8 Gy (RBE) fractions weekly using active raster-scanning intensity modulated proton beam therapy (IMPT). Sequential or simultaneous platinum-based chemotherapy was administered if indicated. The primary endpoint was defined as the lack of any acute ≥grade 3 gastrointestinal (GI) or urogenital (GU) toxicity according to the Common Terminology Criteria for Adverse Events v 4.0 or premature treatment abortion. Secondary endpoints were clinical symptoms and toxicity, quality of life, and PFS. All patients completed IMPT according to the protocol, with a median treatment duration of 43 days (range, 33 to 51 days). No patient developed gastrointestinal or genitourinary toxicity ≥grade 3, and the treatment tolerability rate was 100%. Therefore, the null hypothesis H0: Tolerability Rate ≤80% could be rejected in favor of the alternative hypothesis H1: Tolerability rate >80% using an exact binomial test with a one-sided significance level of α=10% (one-sided P value P=.0059). The median follow-up time after the end of IMPT was 25.1 months (range, 20.2 to 50.3 months). 18 of 25 (75%) patients completed the study follow-up of 24 months. 7 patients had progressive disease. Kaplan-Meier-estimated mean PFS was 39.9 months (95% confidence interval: 33.37 to 46.5 months). Postoperative IMPT is a safe treatment option for cervical and endometrial cancer patients, with only low-grade acute and late toxicities. Larger randomized trials are necessary to further assess the potential of IMPT and improve patient selection.

Prikaz bolesnice sa rakom grlića materice i metastazama u desnoj komori

Introduction. Cardiac metastasis of uterine cervical cancer diagnosed prior to mortality (antemortem) is extremely rare. Case report. A female patient 49 years old was brought to the Emergency Department of the Institute for Treatment and Rehabilitation Niška Banja in cardiac arrest, without a pulse and blood pressure. An electrocardiogram revealed sustained ventricular tachycardia, which was terminated by two DC shocks (100J + 150J). Anamnesis and medical history revealed that she had had her squamous cell carcinoma of the uterine cervix removed and had subsequently received seven out of ten planned cycles of chemotherapy and twenty-eight cycles of radiotherapy. The patient was then transferred to the Coronary Unit, where cardiac ultrasound was performed. A homogenous mass measuring 31 x 50 mm was found in the right ventricle. In view of this, cardiac magnetic resonance imaging was performed. This confirmed the presence of the tumor mass in the right ventricle. Unfortunately, only a month after being discharged from our Institute, the patient was admitted to the Clinic of Neurology due to a loss of consciousness. Computer tomography of endocranium was performed revealing metastatic brain lesions. The patient succumbed to the disease just a couple of months later. Conclusion. We presented a rare case of antemortem diagnosed right ventricle metastases in a patient with uterine cervical cancer. Setting the diagnosis in these patients is a challenge in everyday clinical practice since metastases can produce the clinical picture that masks the real etymology of uterine cervical cancer.

Prognostic value of pretreatment FDG PET/CT in uterine cervical cancer according to two major histologic types: squamous cell carcinoma and adenocarcinoma.

The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types. Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models. SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02). Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type.

Minimally invasive radical hysterectomy and the importance of avoiding cancer cell spillage for early-stage cervical cancer: a narrative review.

Radical hysterectomy is a standard surgery to treat early-stage uterine cervical cancer. The Laparoscopic Approach to Cervical Cancer (LACC) trial has shown that patients receiving minimally invasive radical hysterectomy have a poorer prognosis than those receiving open radical hysterectomy; however, the reason for this remains unclear. The LACC trial had 2 concerns: the learning curve and the procedural effects. Appropriate management of the learning curve effect, including surgeons' skills, is required to correctly interpret the result of surgical randomized controlled trials. Whether the LACC trial managed the learning curve effect remains controversial, based on the surgeons' inclusion criteria and the distribution of institutions with recurrent cases. An appropriate surgical procedure is also needed, and avoiding intraoperative cancer cell spillage plays an important role during cancer surgery. Cancer cell spillage during minimally invasive surgery to treat cervical cancer is caused by several factors, including 1) exposure of tumor, 2) the use of a uterine manipulator, and 3) direct handling of the uterine cervix. Unfortunately, these issues were not addressed by the LACC trial. We evaluated the results of minimally invasive radical hysterectomy while avoiding cancer cell spillage for early-stage cervical cancer. Our findings show that avoiding cancer cell spillage during minimally invasive radical hysterectomy may ensure an equivalent oncologic outcome, comparable to that of open radical hysterectomy. Therefore, evaluating the importance of avoiding cancer cell spillage during minimally invasive surgery with a better control of the learning curve and procedural effects is needed.

Hydrogel spacer injection to the meso-sigmoid to protect the sigmoid colon in cervical cancer brachytherapy: A technical report.

The use of a hydrogel spacer inserted into recto-vaginal fossa is a valuable strategy to mitigate radiation exposure to the rectum during radiation therapy for female pelvic malignancies. However, when the sigmoid colon is in proximity to the cervix, radiation exposure to the sigmoid colon cannot be adequately mitigated with a hydrogel spacer injected into the recto-vaginal fossa. Here, we presented a case, in which a hydrogel spacer was injected into the meso-sigmoid to protect the sigmoid colon. A 73-year-old female diagnosed with T3b stage IIIC2r uterine cervical cancer (FIGO 2018) underwent high-dose-rate interstitial brachytherapy consisting of 24 Gy in 4 fractions, following concurrent chemoradiotherapy with external beam radiation therapy of 50 Gy in 25 fractions of whole pelvic radiation therapy. In the initial brachytherapy, the sigmoid colon was in close contact with the uterine cervix. In the second brachytherapy, attempts to create a space between the sigmoid colon and uterine cervix using injected artificial ascites were unsuccessful due to rapid absorption of fluid. In the third and fourth brachytherapy fractions, 5 mL of hydrogel was injected into the meso-sigmoid through a pouch of Douglas under trans-rectal ultrasonography guidance. Dose ratio of sigmoid colon D2cc and high-risk clinical target volume (HR-CTV) D90 of each brachytherapy were evaluated. Dose ratio of the sigmoid colon D2cc to HR-CTV D90 was 1.03, 0.43, 0.56, and 0.47 in each respective brachytherapy session, indicating dose escalation to HR-CTV whilst achieving acceptable sigmoid dose with hydrogel spacer injected into the meso-sigmoid. The dose ratio of the sigmoid colon to HR-CTV D90 was decreased by introducing a hydrogel spacer into the meso-sigmoid. In cases where the sigmoid colon is in proximity to the cervical tumor, this novel technique can be considered to achieve better clinical outcomes.

Impact of LINC00673 genetic variants on uterine cervical cancer clinicopathologic characteristics.

To date, no study delineates the relationships among the genetic variants of long intergenic noncoding RNA 673 (LINC00673) and uterine cervical carcinogenesis as well as clinicopathological parameters and 5 years survival of cervical cancer patients in Taiwan. Therefore, the involvement of LINC00673 polymorphisms in cervical cancer was investigated. Genotypic frequencies of three LINC00673 polymorphisms rs6501551, rs9914618 and rs11655237 were determined in 199 patients including 115 patients with invasive cancer, 84 with precancerous lesions, and 274 control females using real-time polymerase chain reaction. It revealed that LINC00673 polymorphisms were not found significantly related to development of cervical cancer. Cervical cancer patients with genotypes AG/GG in LINC00673 rs6501551 had more risk to have tumor diameter larger than 4 cm as compared to those with genotype AA (p=0.043). Cervical cancer patients with genotype GG in rs6501551 had worse 5 years survival as compared to those with genotypes AA/AG in multivariate analysis (hazard ratio: 4.70; p=0.097). However, only two patients exhibiting GG were noted, and one had mortality, another had no mortality. In conclusion, larger sample size needs to verify the associations of LINC00673 genetic variants with clinicopathological parameters and patient survival of cervical cancer for Taiwanese females.

Emphysematous pyelonephritis after urinary diversion by percutaneous nephrostomy in patient with advanced cervical cancer: A case report

Emphysematous pyelonephritis is a severe kidney infection that is common in women and patients with diabetes mellitus, but rare in cancer patients. A 64-year-old patient with advanced uterine cervical cancer developed emphysematous pyelonephritis after urine diversion by percutaneous nephrostomy of the left kidney, which is a possible approach to this infection. Antibiotic therapy was started to achieve clinical improvement and preserve renal function, and radical nephrectomy was not an option due to the functional exclusion of the contralateral kidney. The patient progressed with worsening renal function; thus, she started outpatient hemodialysis, with improvement of the uremic encephalopathy. She died 7.7 months after admission, 1 month after treatment for emphysematous pyelonephritis. Treatment should be adjusted to the patients’ needs, including maintenance of hemodialysis to improve symptoms. Further investigation is needed to identify possible causes and prevent emphysematous pyelonephritis in cancer patients.

Incidence and treatment outcomes of uterine cervical cancer in Korea 1999-2018 from the national cancer registry.

To describe the incidence and survival outcomes of uterine cervical cancer during 1999-2018. Patients who were diagnosed with cervical cancer during 1999-2018 were identified in the Korea Central Cancer Registry. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Survival rates by histology, year of diagnosis (1999-2008 vs. 2009-2018), stage, and age at diagnosis were analyzed. The absolute incidence of cervical cancer decreased over 20 years from 4,488 in 1999 to 3,500 in 2018, with an APC of -3.42% (p<0.0001). While ASR of squamous cell carcinoma (SCCA) more than halved from 13.27 per 100,000 in 1999 to 6.16 in 2018 (APC, -4.04%), adenocarcinoma continued to rise (ASR, 1.30 per 100,000 to 1.92; APC, 1.52%; p<0.0001). Patients with adenocarcinoma were younger than those with SCCA (mean, 49.9±12.7 vs. 52.9 ±14.6 years; p<0.0001). Five-year survival rate of cervical cancer patients overall was 78.0%. Adenocarcinoma had poorer survival than SCCA (5-year survival rate, 76.8% vs. 79.8%; p<0.0001). There was no survival difference between patients who were diagnosed between 1999-2008 and 2009-2018. Earlier-stage disease had better survival (5-year survival rate for localized, regional, and distant disease, 90.0% vs. 69.9% vs. 26.5%; p<0.0001). Younger patients aged <50 years had better survival than those aged ≥50 years (87.1% vs. 69.8%; p<0.0001). The incidence of SCCA of the uterine cervix declined while adenocarcinoma continued to increase slowly but significantly from 1999 to 2018 in Korea. Adenocarcinoma was diagnosed at a younger age, but had poorer survival outcome than SCCA.

Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study.

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

Chemotherapy with Bevacizumab for uterine cervical cancer: a multicenter retrospective case-control study

Chemotherapy with Bevacizumab for uterine cervical cancer: a multicenter retrospective case-control study

Bone morphogenetic protein signaling is a possible therapeutic target in gynecologic cancer.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily. BMPs play crucial roles in embryogenesis and bone remodeling. Recently, BMP signaling has been found to have diverse effects on different types of tumors. In this review, we summarized the effects of BMP signaling on gynecologic cancer. BMP signaling has tumor-promoting effects on ovarian cancer (OC) and endometrial cancer (EC), whereas it has tumor-suppressing effects on uterine cervical cancer (UCC). Interestingly, EC has frequent gain-of-function mutations in ACVR1, encoding one of the type I BMP receptors, which are also observed in fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. Little is known about the relationship between BMP signaling and other gynecologic cancers. Tumor-promoting effects of BMP signaling in OC and EC are dependent on the promotion of cancer stemness and epithelial-mesenchymal transition (EMT). In accordance, BMP receptor kinase inhibitors suppress the cell growth and migration of OC and EC. Since both cancer stemness and EMT are associated with chemoresistance, BMP signaling activation might also be an important mechanism by which OC and EC patients acquire chemoresistance. Therefore, BMP inhibitors are promising for OC and EC patients even if they become resistant to standard chemotherapy. In contrast, BMP signaling inhibits UCC growth in vitro. However, the in vivo effects of BMP signaling have not been elucidated in UCC. In conclusion, BMP signaling has a variety of functions, depending on the types of gynecologic cancer. Therefore, targeting BMP signaling should improve the treatment of patients with gynecologic cancer.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer,

IntroductionUterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. MethodWhole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. ResultSerum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. ConclusionsHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

Plasma Cell-Free DNA in Uterine Cervical Cancer: Therapeutic Monitoring and Prognostic Values after Radical Radiotherapy.

In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT). Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months. In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA. Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.