Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. METHODS: The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. RESULTS: A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas.

Serous borderline ovarian tumors (SBOTs) are differentiated, slow growing, noninvasive, and have a better prognosis than their invasive counterparts, but recurrence and progression to invasive carcinomas are common, and unlike high-grade serous carcinomas, they tend to be nonresponsive to chemotherapy. However, due to a lack of culture systems and animal models, information about the properties of SBOT and their changes with neoplastic progression is extremely limited. Our objective was to establish a cell culture model for SBOTs and to characterize their phenotype and genotype. We compared cultures derived from two SBOTs, one of which was a short-term culture containing a BRAF mutation but few other cytogenetic changes while the other culture developed into a spontaneously immortalized permanent cell line and had numerical and structural chromosomal abnormalities but lacked RAS/BRAF mutations. Both cultures formed whorl-like epithelial colonies and resembled low-grade invasive carcinomas by their secretion of CA125 and oviduct-specific glycoprotein, production of matrix metalloproteinases, E-cadherin expression, and telomerase activity. Other characteristics associated with neoplastic transformation, including invasiveness, anchorage-independent growth, and tumorigenicity, were not observed. Importantly, cell motility was reduced in both lines, likely contributing to the lack of invasiveness. The results reveal a striking phenotypic similarity between the two cell lines, regardless of their cytogenetic diversity, which suggests that their characteristic phenotype is regulated to a large degree by epigenetic and environmental factors. In conclusion, we have established the first permanent SBOT cell line, which provides a new model to elucidate the undefined relationship of SBOTs to invasive ovarian carcinomas.

Basal cell carcinoma of the vulva: clinical features and treatment results in 28 patients.

OBJECTIVE: To review our experience and that in the recent literature regarding basal cell carcinoma of the vulva to see whether current management guidelines are appropriate. METHODS: Twenty-eight women with basal cell carcinoma of the vulva were seen over 25 years at the BC Cancer Agency. The clinical-pathologic features were tabulated and the outcome was analyzed. RESULTS: The mean age was 74 years, and almost two-thirds were over the age of 70 at diagnosis. Patients typically presented with an irritation or soreness, with a symptom duration ranging from a few months to several years. Most lesions were confined to the anterior half of the vulva, and 23 of the 28 patients had T1 lesions. Wide local excision was the treatment method used most commonly. Only one patient was known to have died from disease metastasis. Ten women had other basal cell carcinomas, either before or after the diagnosis of their vulvar lesions, and in ten patients 11 other malignancies were diagnosed. CONCLUSION: Basal cell carcinoma of the vulva is an extremely uncommon tumor that rarely metastasizes or spreads. Primary treatment should consist of wide local excision and continued follow-up.

Gestational trophoblastic disease.

OBJECTIVE: To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT). OPTIONS: Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups. OUTCOMES: Improved mortality and morbidity. EVIDENCE: Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C). VALIDATION: These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer.

This prospective, open-label, pilot phase 2 study examined the clinical and immunologic effects of oregovomab (OvaRex) in heavily pretreated patients with recurrent ovarian cancer (OC). Thirteen women were administered intravenous oregovomab (2 mg) at weeks 0, 2, 4, 8, and 12, followed by quarterly doses for up to 2 years or disease progression. Concomitant chemotherapy was not permitted. Eligibility criteria included recurrence after one or more platinum-based chemotherapy regimens, CA125 >35 U/mL, evaluable or measurable disease. Tumor burden was evaluated by physical or radiologic methods pretreatment, weeks 12, 24, and every 24 weeks thereafter. Immune responses, including antibodies and T cells to oregovomab and CA125, were demonstrated in over half the patients. Stabilization of disease and survival >2 years was observed in 3 of 13 patients and coincided with robust immune responses. Shrinkage of marker lesions was not observed; however, four patients showed decreases in CA125 levels. Treatment was well tolerated without serious adverse events or discontinuations due to therapy. This pilot study supports immunologic activity and safety of oregovomab in recurrent OC. Further study of this agent in the consolidation and adjuvant setting is ongoing to establish its clinical utility.

Peritoneal implantation of squamous cell carcinoma following rupture of a dermoid cyst during laparoscopic removal.

BACKGROUND: In recent years, there has been a move toward using laparoscopy in the management of presumed benign ovarian masses. This paper discusses the use of laparoscopy for ovarian masses (particularly dermoid cysts). The focus is on the implications for unexpected malignancies. CASE: We report here a case involving a dermoid cyst that was removed at laparoscopy and was subsequently found to contain a squamous cell carcinoma. Spillage of the cyst's contents occurred at the time of removal. At staging laparotomy, peritoneal implants of the tumor were found, upgrading the tumor from FIGO stage Ia to IIc. CONCLUSION: Spillage rates of dermoid cyst content with laparoscopic removal are inevitably higher than with excision at laparotomy. It remains controversial whether upstaging from FIGO stage Ia to IIc affects prognosis; however, in this case it led to aggressive adjuvant therapy which imposed significant additional morbidity, including loss of fertility, on the patient. One should be aware of the possibility of unexpected malignancy when the decision to manage an ovarian mass laparoscopically is made.

Successful term pregnancy following conservative debulking surgery for a stage IIIA serous low-malignant-potential tumor of the ovary: a case report.

Low-malignant-potential tumors of the ovary can occur in young women of childbearing age. Often these tumors are early stage and confined to the ovary at diagnosis allowing for fertility-preserving surgery. This case report describes a 25-year-old woman who presented with an advanced-stage metastatic LMP tumor and who underwent successful tumor debulking while preserving normal ovarian function. A successful spontaneous pregnancy occurred subsequently and the patient has remained well with 2 years of follow-up.

Clear cell carcinoma arising in extragonadal endometriosis in a caesarean section scar during pregnancy.

Malignancy arising in ectopic endometriosis is a rare event. This paper documents a case of clear cell carcinoma arising in a focus of ectopic endometrium in a low abdominal transverse scar.