Iranian women's psychological responses to positive HPV test result: a qualitative study.

BACKGROUND: Human papillomavirus testing as an established screenings test allow for the early detection and treatment of cervical cancer. Testing positive for HPV may have adverse consequences for women. This study aimed to explore the psychological impacts of testing positive for HPV on women in a developing country with a distinct cultural and religious background. METHODS: Qualitative face-to-face semi-structured interviews were conducted with 40 Iranian women who received a positive high-risk HPV result. Content analysis approach was used to data analysis through MAXQDA10. RESULTS: Three main categories were emerged: initial confrontation; STD-related psychological burden; and rebuilding health. Initial reactions to positive HPV results were shock, unrealistic fear, confusion, distress, and financial concerns. Stigma was manifested in form of self-blame, fear of HPV-disclosure, negative body image, being stigmatized by healthcare providers, and receiving health care anonymously. Refusal to use insurance services showed how evident and powerful the stigma was. Most women reported lifestyles and sexual behaviors modifications to help their immune system to clear HPV; indicating that the screening can work as a valuable opportunity to improve women's physical and sexual health. Regular follow-up, safe sex and a focus on spirituality enable women infected with HPV to take control of the situation. Worrying about other HPV-linked cancers (oropharynx and anal) and fears of partner infection indicated that women consider HPV to be more than just a cause of cervical cancer. CONCLUSIONS: The findings implied to the HPV-positive women's need to support and factual information. Designing and implementing interventions that mitigate the psychological effect of positive HPV test results can highlight the potential benefits of screening for women's health.

Understanding HPV-positive women's needs and experiences in relation to patient-provider communication issues: a qualitative study.

BACKGROUND: HPV testing has been integrated in cervical cancer screening program. Patient-providers relationship is extremely important to improve cervical cancer screening outcomes. This qualitative study aims to understand HPV-positive women's needs and preferences about HCPs and patient-provider communication based on their experiences of accessing primary and specialized care. METHODS: We conducted 40 semi-structured interviews with HPV-positive women. Recorded interviews transcribed and analyzed using conventional content analysis approach. RESULTS: The analysis of the data led to the extraction of three main categories, including: provider's communication and counseling skills, commitment to professional principles, and knowledgeable and competent provider. Women needed understandable discussion about HPV, emotional support and acceptance, receiving HPV-related guidance and advice, and some considerations during clinical appointments. Women needed HCPs to treat them respectfully, gently and with non-judgmental attitude. "Precancerous" and "high-risk" words and watching colposcopy monitor during procedure had made women anxious. Weak referral system and limited interactions among gynecologists and other HCPs highlighted by participants. CONCLUSION: The results of this study, based on the experiences and perceptions of HPV women receiving health care, contain messages and practical tips to healthcare providers at the primary and specialized levels of care to facilitate patient-provider communication around HPV. Providers need to approach the discussion of HPV with sensitivity and take individual needs and preferences into account to improve the HPV-positive women's healthcare experience.

'Does HPV affect my fertility?' Reproductive concerns of HPV-positive women: a qualitative study.

BACKGROUND: Reproductive health changes can occur following infection with Human papillomavirus. HPV is the most prevalent sexually transmitted infection causing a variety of clinical manifestations ranging from warts to cancer. This study aimed to explore the reproductive concerns of women infected with HPV. METHODS: In this qualitative study, we used the conventional content analysis approach, with the aid of MAXQDA.10 software, to analyze data extracted from the face-to-face semi-structured interviews with 20 Iranian HPV-positive women (sampled by maximum variation purposive sampling). The accuracy of this research was ensured according to the four criteria proposed by Guba and Lincoln. RESULTS: Exploring participants' reproductive concerns, three main categories were identified from the interviews including concerns about fertility potential, pregnancy and non-pregnancy reproductive issues. HPV-positive women concerned about reduced female/ male fertility due to HPV, the impact of the HPV on the fetal health, adverse pregnancy outcomes such as miscarriage and preterm delivery, and mother-to-child transmission of HPV during breastfeeding. HPV-positive women with abnormal cytology results were anxious that becoming pregnant or taking hormonal contraception might worsen their abnormalities. Most married women were reluctant to use a condom. Participants requested further information about the potential reproductive risks of the HPV vaccine. They also wanted to know about the safety of HPV vaccine during pregnancy and breastfeeding. CONCLUSIONS: HPV-positive women had some reproductive concerns that should be considered in the designing of educational-consulting interventions. Women need to be better understood and informed about the impact of HPV on their reproductive health. Health care providers may lack knowledge about these specific areas, and they could benefit from additional up-to-date information to address women's reproductive concerns.

Placenta Site Trophoblastic Tumor and Choriocarcinoma from Previous Cesarean Section Scar: Case Reports.

Choriocarcinoma and placental site trophoblastic tumor (PSTT) are rare varieties of gestational trophoblastic disease (GTD). PSTT alone constitutes about 1-2% of all trophoblastic tumors, which presents at early reproductive age and the serum beta-hCG level is much lower than choriocarcinoma. This tumor usually invades the myometrium and its depth of penetration is a prognostic factor. The first case report is regarding a 33-year-old woman with vaginal bleeding 3 months after abortion. The ultrasound exhibited heterogeneous and hypervascular mass related to previous cesarean scar. Serum beta-hCG level was 67 mIU/ml and chemotherapy was administered. However, due to severe vaginal bleeding and no regression in mass size, total abdominal hysterectomy was performed. Histopathological examination and IHC staining confirmed PSTT from previous cesarean section. The second case report is regarding a 33-year-old woman with cervicoisthmic choriocarcinoma, which was mistaken as cesarean scar pregnancy. The ultrasonography and elevated serum beta-hCG level suggested cesarean scar pregnancy. The patient was treated with methotrexate without any effect. Eventually, cervicoisthmic choriocarcinoma was detected after hysterectomy. A diagnostic error was made leading to possible uterus perforation along with incorrect chemotherapy that resulted in a life-threatening condition. It is concluded that PSTT and choriocarcinoma are the two important differential diagnoses of sustained elevated beta-hCG when imaging evidence is also suggestive. Although PSTT and cervicoisthmic choriocarcinoma are rare, they do exist and are on the rise.

Hypofractionated versus standard chemoradiotherapy in the definitive treatment of uterine cervix cancer: interim results of a randomized controlled clinical trial.

PURPOSE: Concurrent chemoradiation has been the mainstay of treatment for cervix cancer. We aimed to evaluate the non-inferiority of hypofractionated chemoradiation. METHODS: This study was designed as a phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial and we report the interim results after 50% accrual. Cervical cancer patients with FIGO stages IIA-IIIC were recruited from April 2021 to September 2022. The intervention consisted of 40 Gy of 3D-conformal radiation therapy (RT) in 15 fractions over 3 weeks. In the control group, patients received standard chemoradiation of 45 Gy in 25 fractions over 5 weeks. Both groups received concurrent weekly cisplatin (40 mg/m2). Intravaginal brachytherapy of 28 Gy in 4 weekly fractions was delivered starting 1 week after the end of chemoradiation. The primary outcome was complete clinical response(CCR) at 3 months. Secondary outcomes included acute gastrointestinal (GI), genitourinary(GU), skin, and hematologic toxicities. A p value less than 0.05 was considered significant for analyses. RESULTS: 59 patients were randomized; 30 in the control group and 29 in the intervention group. 20/30 (66.7%) of the patients in the control group and 19/29 (65.5%) in the intervention group achieved a CCR (absolute difference of 0.011, 95% CI - 0.23 to 0.25, p value: 0.13). There was a significantly higher rate of acute grade ≥ 3 GI toxicity in the intervention group (27.6%) compared with the control group (6.7%) (p value 0.032). CONCLUSIONS: Despite an absolute difference of 1.1% in the 3-month CCR, our interim analysis failed to show the non-inferiority of the hypofractionated chemoradiation. Due to the higher GI toxicities, we will continue this trial using intensity-modulated radiation therapy. REGISTRATION NUMBER AND DATE: ClinicalTrials.gov: NCT04831437, 2021.4.1.

Wnt5A and TGFß1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation.

In this paper, we investigate whether Wnt5A is associated with the TGF-ß1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFß1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased Smad2/3 activation and YAP1 expression and nuclear shuttling in ovarian cancer (OvCa) cells. Furthermore, Wnt5A was required for TGFß1-induced cell migration and invasion. In addition, inhibition of YAP1 transcriptional activity by Verteporfin (VP) altered OvCa cell migration and invasion through decreased Wnt5A expression and inhibition of Smad2/3 activation, which was reverted in the presence of exogenous Wnt5A. We found that the activation of TGFß1 and YAP1 nuclear shuttling was promoted by Wnt5A-induced integrin alpha v. Lastly, Wnt5A was implicated in activating human primary omental mesothelial cells and subsequent invasion of ovarian cancer cells. Together, we propose that Wnt5A could be a critical mediator of EMT-associated pathways.

What are the determinants of parametrial invasion in patients with early stage cervical cancer: A cross sectional study.

Introduction: There was an increase in number of patients presented with early-stage cervical cancer (CC). Tumors with favorable pathological features might be candidates for less radical surgery. Methods: We retrospectively reviewed 700 patients with histologically confirmed CC between January 2011 and March 2020. Chi-square, Fisher's exact tests and multivariate logistic regression analysis were used to assess relations between parametrial involvement (PI) and clinic-pathological variables. Results: Total number of 132 patients with stage IA to IIA were eligible to participate. Squamous cell carcinoma was reported in 100 (75.8%) patients, adenocarcinoma and other tumor pathologies were found in 24(18.2%) and 8(6.1%), respectively. Considering the 2018 FIGO stage, 11 (8.4%) patients had IA, 111 (83%%) IB and 10 (7.6%) IIA. Nine patients (6.8%) had PI on permanent pathologic report. Univariate analysis demonstrated that following variables were statistically different between patients with and without PI: age ≥50, tumor size ≥ 3 cm, lower segment involvement, poorly differentiated pathology, deep stromal invasion, pelvic lymph node, lympho-vascular involvement and positive surgical margin (all p values < 0.05). Among these variables only tumor size ≥3 cm (OR: 2.1, 95% CI: 1.11-4.16, p value: 0.02), deep stromal invasion (OR: 2.2, 95% CI: 1.9-7.43, p value: 0.02) and positive surgical margin (OR: 5.1, 95% CI: 3.97-11.15, p value: 0.008) were independent risk factor of PI in multivariate analysis. Conclusions: Early stage CC might be surgically approached in a more conservative manner if patients have tumor size <3 cm and do not have deep stromal invasion in conization.

The Outcome of Locally Advanced Cervical Cancer in Patients Treated with Neoadjuvant Chemotherapy Followed by Radical Hysterectomy and Primary Surgery.

Background: In recent years, before radical hysterectomy, neoadjuvant chemotherapy (NACT) has been administered to patients with locally advanced cervical cancer to shrink large tumors. It has been reported that this treatment significantly reduces the need for radiotherapy after surgery. The current study aimed to assess the outcome (survival, recurrence, and the need for adjuvant radiotherapy) of locally advanced cervical cancer in patients treated with NACT followed by radical hysterectomy and primary surgery. Methods: In a retrospective cohort study, the records of 258 patients with cervical cancer (stage IB2, IIA, or IIB), who referred to Imam Khomeini Hospital (Tehran, Iran) from 2007 to 2017 were evaluated. The patients were assigned into two groups; group A (n=58) included patients, who underwent radical hysterectomy and group B (n=44) included those, who underwent a radical hysterectomy after NACT. The outcome measures were the recurrence rate, five-year survival rate, and the need for adjuvant radiotherapy. Results: The median for overall survival time in group A and B was 113.65 and 112.88 months, respectively (P=0.970). There was no recurrence among patients with stage IB2 cervical cancer in group B, while the recurrence rate in group A was 19.5% with a median recurrence time of 59.13 months. Lymph node involvement was the only factor that affected patients' survival. The need for postoperative adjuvant radiotherapy in group B was lower than in group A (P=0.002). Conclusion: NACT before the hysterectomy was found to reduce the need for postoperative radiotherapy in patients with locally advanced cervical cancer according to disease stages. As a direct result, adverse side effects and the recurrence rate were reduced, and the overall survival rate of patients with stage IIB cervical cancer was increased.

A Diagnostic Algorithm using Multi-parametric MRI to Differentiate Benign from Malignant Myometrial Tumors: Machine-Learning Method.

This study aimed to develop a diagnostic algorithm for preoperative differentiating uterine sarcoma from leiomyoma through a supervised machine-learning method using multi-parametric MRI. A total of 65 participants with 105 myometrial tumors were included: 84 benign and 21 malignant lesions (belonged to 51 and 14 patients, respectively; based on their postoperative tissue diagnosis). Multi-parametric MRI including T1-, T2-, and diffusion-weighted (DW) sequences with ADC-map, contrast-enhanced images, as well as MR spectroscopy (MRS), was performed for each lesion. Thirteen singular MRI features were extracted from the mentioned sequences. Various combination sets of selective features were fed into a machine classifier (coarse decision-tree) to predict malignant or benign tumors. The accuracy metrics of either singular or combinational models were assessed. Eventually, two diagnostic algorithms, a simple decision-tree and a complex one were proposed using the most accurate models. Our final simple decision-tree obtained accuracy = 96.2%, sensitivity = 100% and specificity = 95%; while the complex tree yielded accuracy, sensitivity and specificity of 100%. To summarise, the complex diagnostic algorithm, compared to the simple one, can differentiate tumors with equal sensitivity, but a higher specificity and accuracy. However, it needs some further time-consuming modalities and difficult imaging calculations. Trading-off costs and benefits in appropriate situations must be determinative.

Vulvar cancer in Iran: Retrospective study over 20 years (1998-2018).

BACKGROUND: We did not have any data about vulvar cancer - as a fourth cause of gynecological cancer in the worldwide - in our country. STUDY DESIGN: Our study is designed to evaluate the frequency, stage and outcome of patients with vulvar cancer. MATERIALS AND METHODS: In this retrospective observational study, we studied patients' records with diagnosis of vulvar cancer who referred to department of gynecology oncology, Emam-Khomeini Hospital (EKH), Tehran, Iran, between January 1998 and December 2018. A total of 106 cases of vulvar cancers were found in the records of outpatient oncology clinic of medical university of Tehran university. Survival was estimated using the Kaplan-Meier analysis with SPSS version of 24. RESULTS: Mean age of the 106 patients in the study was 59.2 years. The most site of tumor involvement was major labial (39.1%). Vulvar cancer significantly was more in multiparous (P < 0.001) and menopause patients (P < 0.001). Squamous Cell Carcinoma was the most pathology of vulvar cancer (72.2%). Ninety patients (84.9%) had surgery as a primary treatment and 48 (53.3%) of these patients received adjuvant radiotherapy or chemoradiation after surgery. Mean duration of patient's follow up was 82.4 ± 68.3 month. Five-year survival of our patients in all stages was 71%. CONCLUSIONS: Our findings are located between developed and underdeveloped countries. Our patients are diagnosed nearly in earlier stages of disease and 84.9%t of them had surgery as a primary treatment, so earlier surgery resulted in good survival of patients.