Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer.

OBJECTIVE: Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen  compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. METHODS: Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for  HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. RESULTS: Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. CONCLUSION: HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Management of inoperable endometrial cancer.

Some endometrial cancer (EMC) patients are not good candidates for primary surgery. The three major types of treatment for inoperable EMC are radiation therapy, chemotherapy, or their combination as neoadjuvant treatment before surgery. Radiation therapy alone (of different modes) has been used as the sole definitive therapeutic modality, particularly for early-stage disease that is limited to the uterine body and cervix with or without parametrial invasion. The most common treatment modality is neoadjuvant treatment before surgery. Postoperative adjuvant treatment is also occasionally used, depending mainly on the sites of the disease and the results of surgery. Data on neoadjuvant hormonal or radiation therapy are limited, with studies focusing on laboratory outcomes or having only a small number of patients. Most neoadjuvant treatments before surgery involved chemotherapy and fewer combined chemoradiotherapy. Surgery was generally performed, particularly in patients who had shown responses or at least stable disease to neoadjuvant treatment. Perioperative outcomes after neoadjuvant treatment were superior to those after primary surgery, whereas survival data were still inconsistent. Features that had or tended to have a favorable prognosis were younger age, early-stage disease, response to neoadjuvant treatment, low preoperative cancer antigen-125 level, and optimal surgery. Among different modalities of neoadjuvant treatment, which has become a frequent mode of treatment, neoadjuvant chemotherapy was more common than radiation therapy alone or chemoradiation.

Rapid and ultrasensitive detection of circulating human papillomavirus E7 cell-free DNA as a cervical cancer biomarker.

Circulating cell-free DNA (cfDNA) has attracted attention as a non-invasive biomarker for diagnosing and monitoring various cancers. Given that human papillomavirus (HPV) DNA integration and overexpression of E6/E7 oncogenes are pivotal events for carcinogenesis, we sought to determine if HPV E7 cfDNA could serve as a specific biomarker for cervical cancer detection. We applied droplet digital PCR (ddPCR) to quantify HPV16/18 E7 cfDNA from the serum of patients with cervical cancer, cervical intraepithelial neoplasia, and controls. HPV16/18 E7 cfDNA was highly specific for cervical cancer, displaying 30.77% sensitivity, 100% specificity, and an area under the curve of 0.65. Furthermore, we developed a sensitive isothermal detection of HPV16/18 E7 and the PIK3CA WT reference gene based on recombinase polymerase amplification combined with a lateral flow strip (RPA-LF). The assay took less than 30 min and the detection limit was 5-10 copies. RPA-LF exhibited 100% sensitivity and 88.24% specificity towards HPV16/18 E7 cfDNA in clinical samples. The agreement between RPA-LF and ddPCR was 83.33% (κ = 0.67) for HPV16 E7 and 100% (κ = 1.0) for HPV18 E7, indicating a good correlation between both tests. Therefore, we conclude that HPV E7 cfDNA represents a potential tumor marker with excellent specificity and moderate sensitivity for minimally invasive cervical cancer monitoring. Moreover, the RPA-LF assay provides an affordable, rapid, and ultrasensitive tool for detecting HPV cfDNA in resource-limited settings.

Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients.

BACKGROUND: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. MATERIALS AND METHODS: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. RESULTS: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinum- sensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. CONCLUSIONS: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.

Vulvar pseudoepitheliomatous hyperplasia associated with herpes simplex virus type II mimicking cancer in an immunocompromised patient.

We report an exaggerated dermatological inflammatory condition in an immunocompromised patient. The patient was a 51-year-old woman who had HIV infection and a history of cervical cancer. Three years after highly active antiretroviral therapy with an improved immune status, and 2 years after remission of cervical cancer, she developed verrucous perineal masses. Provisional diagnosis was recurrent cervical cancer or primary vulvar cancer. Pathological features revealed pseudoepitheliomatous hyperplasia associated with herpes viral infection. After minimal response to systemic oral antiviral drugs and topical imiquimod, she had clinical resolution with the addition of systemic oral corticosteroid.