Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study.

BACKGROUND: Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23. METHODS AND FINDINGS: Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+. CONCLUSION: Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. TRIAL REGISTRATION: Trial registration number: NCT0304955.

Adenocarcinoma In Situ of the Uterine Cervix (AIS) Treated by Loop Electrosurgical Excision Procedure Strategy: An Observational Study.

OBJECTIVES: Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy. METHODS: Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment. RESULTS: A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures. CONCLUSION: The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.

Indeterminate thyroid cytology in an iodine-deficient population: Prevalence, operation rate, risk of malignancy anddiagnostic value of thyroid scintigraphy and 18F-FDG PET imaging parameters.

OBJECTIVE: Patients with indeterminate thyroid cytology often have a diagnostic hemithyroidectomy. The role of molecular imaging, particularly fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), is controversial, and demographic variations in tumor prevalence and histology influence test performance and clinical utility. We retrospectively assessed the prevalence of indeterminate thyroid cytology and the malignancy rate in patients from an iodine deficient area, and evaluated the diagnostic value of preoperative thyroid scintigraphy and 18F-FDG PET/CT among operated patients. SUBJECTS AND METHODS: From 2006-2018, all patients with indeterminate thyroid cytology from the North Denmark region were included in the study (population 600,000).Clinical data, including operation rate, preoperative molecular imaging, and histopathological diagnosis, were retrieved. The results from preoperative thyroid scintigraphy and 18F-FDG PET/CT-scanning were compared to the final histopathological diagnosis. RESULTS: Four hundred and thirty-three patients were found with indeterminate thyroid cytology.The main registered reasons for conducting a fine needle aspiration biopsy (FNAB) were "cold nodule", goiter or a palpable nodule (n=312). In 40 patients (9%), FNAB was registered as conducted due to a PET incidentaloma. Four hundred and two patients (93%) underwent diagnostic lobectomy, and this population formed the study population for the following explorative study: One-hundred and two patients (25%) had a malignant diagnosis. In 226 (56%) and 51 (25%) patients, respectively, preoperative thyroid scintigraphy and 18F-FDG PET/computed tomography (CT) was performed. Among patients with a final malignant disease who had a thyroid scintigraphy (40 patients), a cold nodule was seen in 90% of cases; one (atypical) patient presented a warm nodule. Among patients with a final malignant disease 16 patients (16%) had a 18F-FDG PET (incl. 3 missing PET scans). Among the 51 patients with preoperative 18F-FDG PET/CT, no difference in the PET-derived parameters was found between benign (n=33) and malignant tumors (n=13). CONCLUSION: The prevalence of malignancy (25%) was comparable with that in other studies. In patients with a preoperative thyroid scintigraphy, 90% of malignant cases had a cold nodule on scintigraphy. In patients with a preoperative PET/CT-scanning presenting focal 18F-FDG-uptake, PET-derived parameters had no diagnostic value. However, the diagnostic value of 18F-FDG-avidity vs. non-avidity needs to be addressed prospectively.

Follow-up After Loop Electrosurgical Excision of Cervical Intraepithelial Neoplasia: The Use of Combined Cytology and Human Papillomavirus Testing.

OBJECTIVES: The aims of the study were to investigate how many women after 1 or 2 follow-up examinations, based on combined cervical cytology and human papillomavirus (HPV) testing, could finish posttreatment follow-up and continue with the general screening program and to determine the 5-year risk of recurrence in this group. METHODS: This is a prospective observational study that includes women, who underwent loop electrosurgical excision procedure (LEEP) in the North Denmark Region, from January 1, 2012, to May 31, 2014. All included women had histologically verified diagnosis of high-grade cervical intraepithelial neoplasia (CIN 2+) or adenocarcinoma in situ (AIS) before LEEP and posttreatment follow-up with cervical cytology and HPV combination testing. Study period was until October 2019. RESULTS: Totally, 563 women were included in the study. After finishing the posttreatment follow-up, 439 (78%) could continue to the general screening program and 362 of them had a screening during the study period. Six women (1.7%) had either cervical dysplasia and/or HPV infection in the cervical screening, and of these, 3 (0.8%) had high-grade dysplasia corresponding to CIN 2. None was diagnosed with CIN 3, AIS, or invasive carcinoma. One hundred twenty-one women (36%) chose to be screened sooner than recommended in the national guidelines. CONCLUSIONS: Human papillomavirus and cytology combination test after LEEP allows women, irrespective of margin status, safely to continue with the general screening program after a short posttreatment follow-up period. Improved information is mandatory to reduce "opportunistic" screening after finishing posttreatment follow-up.

Spontaneous utero-cutaneous fistula between a benign uterine leiomyoma and abdominal skin: A case report.

The case of a 56-year-old woman with a fibroid uterus who developed utero-cutaneous fistula is presented. The woman was para 0, had an unremarkable medical history, and had no prior diagnosis of a gynecologic pathology, no operative interventions involving the uterine wall or any other risk factor for fistula. Abdominal examination revealed an abdominal mass with overlying deep, purulent ulceration. 18F-FDG PET/CT scan was consistent with uterine leiomyoma, but a differential diagnosis of sarcoma was considered due to the presence of the fistula, patchy increased FDG uptake of the tumor and several mildly enlarged lymph nodes bilaterally in the inguinal and iliac region. Hysterectomy with bilateral salpingo-oophorectomy was performed. Histological diagnosis was of leiomyoma with focal bizarre atypia, degenerative and metaplastic changes and utero-cutaneous fistula. To the best of our knowledge, this is the first case report describing a benign leiomyoma forming a fistula between the uterus and abdominal surface.