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We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.
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With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
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Infecciones por Papillomavirus , Médicos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Virus del Papiloma Humano , Detección Precoz del Cáncer/métodos , Papillomaviridae/genética , Manejo de Especímenes/métodos , Frotis Vaginal/métodos , Sensibilidad y EspecificidadRESUMEN
Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.
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Alphapapillomavirus/genética , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Alphapapillomavirus/patogenicidad , Conización , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Prueba de Papanicolaou , Estudios Prospectivos , Taiwán , Resultado del Tratamiento , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/virologíaRESUMEN
PURPOSE: To investigate the prognostic factors and impact of adjuvant treatment on uterine carcinosarcoma (UCS). METHODS: A retrospective review of UCS patients treated between 2005 and 2019 was conducted. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system was used. Multivariate stepwise Cox proportional hazard regression models were used to identify the independent predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients were eligible for descriptive analysis. Excluding 12 patients without surgery, 126 patients with adequate clinicopathologic data were included for prognostic analysis. The median follow-up for survivors was 51.8 months. 5-year OS and PFS rates for FIGO stage I, II, III, IV were 64.5% and 51.8%, 60.8% and 57.7%, 47.7% and 45.9%, 5.1% and 4.1%, respectively. By multivariate analysis, six models each for PFS and OS were formulated including highly correlated variables alternatively. Adjuvant chemoradiation was consistently selected as an independent prognostic factor for OS (hazard ratio [HR] 0.10-0.22, all p < 0.001) and PFS (HR 0.12-0.23, all p < 0.001), while adjuvant chemotherapy (HR 0.33-0.41), age≥58 years (HR 1.80-1.91), stage III/IV (HR 3.36-13.34), and adnexal metastasis (HR 2.06-5.02) in three to four of the six models for OS. Stratified analyses revealed that adjuvant chemoradiation significantly improved outcome compared with adjuvant chemotherapy for stage IA patients with lymphovascular space invasion and stage IB-IV, lymph node metastasis, and adnexal metastasis. CONCLUSION: Adjuvant chemoradiation was confirmed as an independent good prognostic factor, while older age, stage III/IV, and adnexal metastasis were associated with poor outcome in UCS.
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Carcinosarcoma , Neoplasias Uterinas , Anciano , Carcinosarcoma/patología , Carcinosarcoma/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapiaRESUMEN
BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. METHODS: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). RESULTS: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS. CONCLUSION: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.
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Adenocarcinoma de Células Claras/terapia , Recurrencia Local de Neoplasia/terapia , Neoplasias Ováricas/terapia , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Pronóstico , Tasa de Supervivencia , Taiwán , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Assessment of tumor extent and lymphatic metastasis of uterine carcinosarcomas is important for treatment planning. PURPOSE/HYPOTHESIS: To evaluate the diagnostic accuracy of 3.0T diffusion-weighted (DW) MRI for patients with uterine carcinosarcoma, in assessment of tumor extent and lymphatic metastasis. STUDY TYPE: Retrospective diagnostic accuracy study. POPULATION: A consecutive cohort of 68 patients with pathologically proved carcinosarcoma between January 2006 and July 2014. FIELD STRENGTH/SEQUENCE: 3T DW MRI. ASSESSMENT: Maximal tumor and uterus size, presence of deep myometrial invasion, cervical invasion, adnexal invasion, lymphadenopathy, and the apparent diffusion coefficient (ADC) values of each tumor were used. Histopathology was the gold standard. STATISTICAL TESTS: Diagnostic accuracy. Logistic regression. RESULTS: In all, 38 patients entered the final analysis, with median age of 58 years (range, 35-79 years). The sensitivity and specificity in detecting deep myometrial invasion, cervical stromal invasion, adnexal invasion, as well as pelvic and para-aortic lymph node metastases were 65% and 72%, 91% and 85%, 50% and 100%, 33% and 89%, and 33% and 100%, respectively. The largest tumor diameters predicted deep myometrium invasion (anteroposterior direction, P = 0.004) and cervical stroma invasion (craniocaudal direction, P = 0.008). Tumor ADCmin significantly predicted the lymphovascular permeation (P = 0.025; odds ratio = 0.96). DATA CONCLUSION: Preoperative DW MRI is useful to assess deep myometrial or cervical stromal invasion in uterine carcinosarcoma, yet the diagnostic performance for detecting adnexal invasion and lymphatic metastasis requires further improvement. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
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OBJECTIVES: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas. METHODS: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays. RESULTS: Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors. CONCLUSION: Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.
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Carcinoma Endometrioide/genética , Variaciones en el Número de Copia de ADN , Neoplasias Endometriales/genética , Neoplasias Primarias Múltiples/genética , Neoplasias Ováricas/genética , Adulto , Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Mutación , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patologíaRESUMEN
BACKGROUND/PURPOSE: Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. METHODS: Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. RESULTS: Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable. CONCLUSION: Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.
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Tamizaje Masivo/psicología , Infecciones por Papillomavirus/diagnóstico , Aceptación de la Atención de Salud/psicología , Autocuidado/psicología , Frotis Vaginal/psicología , Adulto , Femenino , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Prueba de Papanicolaou/estadística & datos numéricos , Papillomaviridae , Estudios Prospectivos , Autocuidado/métodos , Encuestas y Cuestionarios , Taiwán , Frotis Vaginal/métodos , Adulto JovenRESUMEN
BACKGROUND: Previous studies assessing second primary malignancies (SPMs) after uterine cancer have been conducted in Western populations with conflicting results. This study aimed to define the incidence and risk of SPMs in Taiwanese patients with an initial diagnosis of uterine cancer. METHODS: Using population-based data from the Taiwan Cancer Registry for the period 1979-2008, we quantified standardized incidence ratios (SIRs) among 11,571 women with an initial diagnosis of uterine cancer. RESULTS: Among the 11,571 women, 555 (4.80%) developed at least one SPM during 69,987 person-years of follow-up. There was a 71% increased risk of SPM following uterine cancer (SIR=1.71, 95% CI, 1.57-1.86), with higher risks in the vagina/vulva (SIR=9.06), small intestine (SIR=8.45), ovary (SIR=4.15), urinary bladder (SIR=2.31), kidney (SIR=2.24), colorectum (SIR=2.24), lung (SIR=1.96), and breast (SIR=1.43). The risk of SPM was found to be the highest within the first 5 years after diagnosis of uterine cancer, with surveillance bias possibly contributing to the extremely high risk observed in the first follow-up year. The overall risk and pattern of SPM development observed in this study differed from those previously reported in Western populations, possibly because of the methodology and shorter follow-up period employed in this study. The cumulative incidence of SPMs was significantly higher in older patients (≥50 years) than in younger patients (P<0.001). CONCLUSIONS: To our knowledge, this is the first study in an Asian population to report 71% increased risk in SPMs in women previously diagnosed with uterine cancer. A younger age at diagnosis of uterine cancer conferred an increased risk of second malignancies, and SPMs worsened survivorship in patients who survived uterine cancer.
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Pueblo Asiatico/estadística & datos numéricos , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Uterinas/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Sistema de Registros , Medición de Riesgo , Tasa de Supervivencia , Taiwán/epidemiología , Factores de Tiempo , Neoplasias Uterinas/diagnósticoRESUMEN
OBJECTIVE: To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. METHODS: We reviewed the medical records and histological files of 144 patients with FIGO stages IA-IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. RESULTS: There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P=0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy (n=14, including 12 stages IB2-IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery (n=97, including 40 stages IB2-IIB) (P=0.046). CONCLUSIONS: None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I-II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.
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Carcinoma de Células Pequeñas/radioterapia , Carcinoma de Células Pequeñas/cirugía , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Pequeñas/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Taiwán , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. METHODS: Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40mg/m(2) and gemcitabine 125mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. RESULTS: An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p=0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p=0.89), but crossed over at 5years. Grade 2-4 hematological toxicities, including neutropenia (p=0.028) and thrombocytopenia (p=0.001), were more frequent in arm CG than arm C. CONCLUSIONS: Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , GemcitabinaRESUMEN
OBJECTIVES: To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar malignancies. METHODS: Abdominal and pelvic CT/MRI and whole-body (18) F-FDG (fluorodeoxyglucose) PET or PET/CT (collectively designated PET hereafter) were performed. Lesion status was determined by the pathological findings or clinical follow-up. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The clinical impact of PET was determined on a per scan basis. RESULTS: Twenty-three patients were enrolled, and 38 PET examinations were performed. CT/MRI and PET studies were used for primary staging (n = 17), monitoring the response (n = 7) and restaging after recurrence (n = 14). In primary staging, there was no significant difference between CT/MRI and PET in detecting metastatic inguinal lymph nodes (ILN). CT/MRI was significantly more efficacious than PET in detecting pelvic lymph node (PLN) or distant metastasis (p = 0.007 by ROC per patient basis). PET findings resulted in two positive impacts and one negative impact for both primary staging and restaging. CONCLUSIONS: False-positive PLN or distant metastasis PET findings are not uncommon, and hence should be interpreted with caution. PET can be supportive when metastatic ILN/PLN or distant metastasis is suspected on CT/MRI. KEY POINTS: ⢠False-positive metastatic PLN or distant metastasis PET findings are not uncommon. ⢠CT/MRI has value in the management of vulvar malignancies. ⢠PET can be supportive when metastasis is suspected by CT/MRI.
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Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Vulva/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Imagen Multimodal , Estudios Prospectivos , Radiofármacos , Reproducibilidad de los Resultados , Vulva/diagnóstico por imagen , Vulva/patologíaRESUMEN
OBJECTIVE: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. METHODS: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. RESULTS: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1-23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2-97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6-121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9-121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53-7.60; P = 0.003), type II histology (HR, 2.50; 1.28-4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07-4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30-4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. CONCLUSIONS: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.
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Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/terapia , Cistadenocarcinoma Seroso/terapia , Neoplasias Endometriales/terapia , Recurrencia Local de Neoplasia/terapia , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Insuficiencia del TratamientoRESUMEN
Current tools are insufficient for distinguishing patients with ovarian cancer from those with benign ovarian lesions before extensive surgery. The present study utilized a readily accessible platform employing a negative selection strategy, followed by flow cytometry, to enumerate circulating tumor cells (CTCs) in patients with ovarian cancer. These counts were compared with those from patients with benign ovarian lesions. CTC counts at baseline, before and after anticancer therapy, and across various clinical scenarios involving ovarian lesions were assessed. A negative-selection protocol we proposed was applied to patients with suspected ovarian cancer and prospectively utilized in those subsequently confirmed to have malignancy. The protocol was implemented before anticancer therapy and at months 3, 6, 9 and 12 post-treatment. A cut-off value for CTC number at 4.75 cells/ml was established to distinguish ovarian malignancy from benign lesions, with an area under the curve of 0.900 (P<0.001). In patients with ovarian cancer, multivariate Cox regression analysis revealed that baseline CTC counts and the decline in CTCs within the first three months post-therapy were significant predictors of prolonged progression-free survival. Additionally, baseline CTC counts independently prognosticated overall survival. CTC counts obtained with the proposed platform, used in the present study, suggest that pre-operative CTC testing may be able to differentiate between malignant and benign tumors. Moreover, CTC counts may indicate oncologic outcomes in patients with ovarian cancer who have undergone cancer therapies.
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Cervical cancer is a significant public health concern, particularly in low- and middle-income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21-65 from three medical centers in Taiwan. The findings indicated that the self-sampling kit was as effective as physician-collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self-sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self-sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.
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ABBREVIATIONS: AMPK: AMP-activated protein kinase; CHX: cycloheximide; RAD001: everolimus; HBSS: Hanks' balanced salt solution; LC-MS/MS: liquid chromatography-mass spectrometry/mass spectrometry; MMP14: matrix metallopeptidase 14; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; PtdIns3P: phosphatidylinositol-3-phosphate; PX: phox homology; SH3: Src homology 3; SH3PXD2A/TKS5: SH3 and PX domains 2A; SH3PXD2A-[6A]: S112A S142A S146A S147A S175A S348A mutant; ULK1: unc-51 like autophagy activating kinase 1.
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Autofagia , Neoplasias Ováricas , Humanos , Femenino , Cromatografía Liquida , Metaloproteinasa 14 de la Matriz , Espectrometría de Masas en Tándem , Proteínas Quinasas Activadas por AMP/metabolismo , Movimiento Celular , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Adaptadoras del Transporte Vesicular , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.
Asunto(s)
Neoplasias Ováricas , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/complicaciones , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Virilismo/complicaciones , Virilismo/diagnóstico , Hipoxia/complicaciones , EsteroidesRESUMEN
BACKGROUND: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. METHODS: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). CONCLUSIONS: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.
Asunto(s)
Carcinoma , ADN Tumoral Circulante , Neoplasias Ováricas , Humanos , Femenino , ADN Tumoral Circulante/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Mutación/genética , Pronóstico , Periodo Posoperatorio , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genéticaRESUMEN
There are limited data on the prevalence and distribution of human papillomavirus (HPV) genotypes in vaginal intraepithelial neoplasia (VAIN). We sought to clarify this issue in a series of 450 VAIN cases with a confirmed diagnosis between 1990 and 2006. HPV genotyping was performed using paraffin-embedded specimens and polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR and direct sequencing. The HPV genotypes of the vaginal and cervical neoplasms were compared for those with incident VAIN and a history of previous/concomitant cervical neoplasms. Ki-67 was performed for supporting diagnosis of VAIN. Of these 450 VAIN cases (median age, 59 years; range, 19-93), two with missing paraffin blocks and 54 with poor DNA quality were excluded. HPV was detected in 273/394 (69.3%) VAIN, and multiple infections were found in 17.9% of HPV-positive samples. The leading types were HPV16 (35.5%), HPV58 (9.9%), HPV52 (9.9%), HPV39 (8.4%), HPV33 (7.3%) and HPV53 (7.0%). Among the 156 cases with a history of previous cervical neoplasia, 29.0% had concordant HPV genotypes, while synchronous VAIN samples (n = 49) were more likely to harbor concordant genotypes (58.7%) with the concomitant cervical neoplasm (p = 0.0003). Whether those HPV types in the incident VAIN lesions had existed in the vaginal epithelium at the time of the previous cervical neoplasia or a new acquisition needs to be clarified in prospective follow-up studies.
Asunto(s)
Alphapapillomavirus/clasificación , Alphapapillomavirus/genética , Carcinoma in Situ/virología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Neoplasias Vaginales/virología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Carcinoma in Situ/epidemiología , ADN Viral/análisis , Femenino , Humanos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Análisis de Secuencia de ADN , Neoplasias del Cuello Uterino/epidemiología , Neoplasias Vaginales/epidemiología , Adulto JovenRESUMEN
Endometrial cancer (EC) usually presented as a localized disease at diagnosis (67%), 20% of patients diagnosed with regional spread, and distant metastasis accounted for 9%. The standard treatments include hysterectomy, bilateral salpingo-oophorectomy, and pelvic with/without paraaortic lymph node dissection/biopsy. Adjuvant therapy is arranged according to risk factors and stages. Risk group classification varied among different guidelines and studies and evolved with time. Adjuvant modalities include chemotherapy, radiotherapy, chemoradiotherapy, antiangiogenesis agents, immune checkpoint inhibitors, and multi-target agents. We review the recent literature to incorporate important advances in trial results, real-world big data, and knowledge in biomarkers of EC to update appropriate adjuvant therapy and post-surgical treatment of EC patients.