Bandit Chumworathayi

Differential methylation of E2 binding sites in episomal and integrated HPV 16 genomes in preinvasive and invasive cervical lesions

Enhanced expression of the HPV 16 E6‐E7 oncogenes may trigger neoplastic transformation of the squamous epithelial cells at the uterine cervix. The HPV E2 protein is a key transcriptional regulator of the E6‐E7 genes. It binds to four E2 binding sites (E2BSs 1–4) in the viral upstream regulatory region (URR). Modification of E2 functions, for example, by methylation of E2BSs is hypothesized to trigger enhanced expression of the viral E6‐E7 oncogenes. In the majority of HPV‐transformed premalignant lesions and about half of cervical carcinomas HPV genomes persist in an extra‐chromosomal, episomal state, whereas they are integrated into host cells chromosomes in the remaining lesions. Here we compared the methylation profile of E2BSs 1–4 of the HPV 16 URR in a series of 18 HPV16‐positive premalignant lesions and 33 invasive cervical cancers. CpGs within the E2BSs 1, 3, and 4 were higher methylated in all lesions with only episomal HPV16 genomes compared with lesions displaying single integrated copies. Samples with multiple HPV16 integrated copies displayed high methylation levels for all CpGs suggesting that the majority of multiple copies were silenced by extensive methylation. These data support the hypothesis that differential methylation of the E2BSs 1, 3 and 4 is related to the activation of viral oncogene expression in cervical lesions as long as the viral genome remains in the episomal state. Once the virus becomes integrated into host cell chromosomes these methylation patterns may be substantially altered due to complex epigenetic changes of integrated HPV genomes.

Feasibility of community-based careHPV for cervical cancer prevention in rural Thailand.

Objective This study aimed to assess the safety, acceptability and feasibility of primary human papillomavirus (HPV) testing for cervical cancer prevention at the community level in a low-resource setting. Materials and Methods After training a technician to run specimens on the careHPV unit, the study team traveled to a different village each day in rural Roi-et Province, Thailand. Women were tested for HPV using self-swab, followed by careHPV testing. Those with positive result were assessed immediately by visual inspection with acetic acid. Women positive for HPV and visual inspection with acetic acid were offered cryotherapy. Safety was determined by monitoring adverse events. Exit surveys assessed acceptability and feasibility. Feasibility was also assessed by measuring testing and triage throughputs. Results Technician training required 2.5 days to achieve competency. A total of 431 women were screened in 14 days, with an average of 31 women screened daily. No adverse events were reported. Women deemed the program overwhelmingly acceptable: 90.5% reported that they would take the self-swab again, 71.3% preferred the self-swab to a clinician swab. The program was also feasible: 99.8% of eligible women agreed to testing, 94.8% returned for same-day follow-up, and women only spent 30 to 50 minutes of their total time with the program from screening to results. Conclusions Cervical cancer prevention programs based on self-swab HPV testing could be safe, acceptable, feasible, and effective at the community level in low-resource settings.

Knowledge and Attitudes toward Palliative Terminal Cancer Care among Thai Generalists

BACKGROUND Our objective was to determine the knowledge and attitudes of Thai generalists (general physicians) toward palliative terminal cancer care (PC) in a primary care setting. MATERIALS AND METHODS We performed a cross-sectional descriptive survey using a self-administered questionnaire. The total number of completed and returned questionnaires was 63, giving a 56% response rate. Data analysis was based on these (Cronbachs alpha=0.82) and percentages and mean values were assessed using the Fishers exact test to determine the correlation of variables. RESULTS Overall, attitude and knowledge levels were slightly satisfactory. Results indicated that general physicians had moderate scores in both attitudes (84.1%) and knowledge (55.7%) regarding palliative terminal cancer care. However, they had insufficient knowledge regarding truth telling, pain control and management with morphine, emergency management in terminal cancer care and treatment of fluid intake in terminal stages. Attitude and knowledge scores were statistically correlated (p=0.036). Knowledge scores were further positively associated with being taught palliative care in their medical curriculum (p=0.042). CONCLUSIONS Formal education in palliative care and development of palliative care services are very much needed in Thailand to provide holistic care to terminally ill patients.

Effect of single-visit VIA and cryotherapy cervical cancer prevention program in Roi Et, Thailand: A preliminary report

Aim:  To assess the effect of introducing visual inspection with acetic acid and cryotherapy on cervical cancer incidence rates in Roi Et province over time, between 1997 and 2006, and compare this with two nearby provinces.

Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions.

To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy‐confirmed cervical low‐grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation).

Visual inspection with acetic acid test qualities in a secondary setting.

Aim:  To evaluate the visual inspection using acetic acid (VIA) test qualities in a secondary (follow‐up) setting, 1 year after cryotherapy treatment performed as part of the Safety, Acceptability and Feasibility demonstration project designed to evaluate the safety, acceptability and feasibility of VIA. An immediate offer of cryotherapy was made to those who test positive and are eligible for treatment.

Elevated preoperative platelet to lymphocyte ratio associated with decreased survival of women with ovarian clear cell carcinoma.

This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies.

Factors Associated with Decisions to Attend Cervical Cancer Screening among Women Aged 30-60 Years in Chatapadung Contracting Medical Unit, Thailand

BACKGROUND This study aimed to identify factors associated with womens decisions to attend cervical cancer screening and to explore those linked with intention to attend in the coming year and to continue regular screening. MATERIALS AND METHODS A community based case-control study was conducted among woman 30-60 years of age in catchment area of Chatapadung Contracting Medical Unit (CCMU), networking of Khon Kaen Center Hospital, Thailand. Self-administered questionnaires were used to collect data, and in-depth interviews were then performed to explore in greater detail. RESULTS There were 195 participants. Only one third (32.3 %) had been screened for cervical cancer within the past 5 years. Some 67.7% reported that they had not been screened because they had no abnormal symptoms, single marital status, and no children. Only 10.6% of those never had screening intent to be screened within the next 12 months. High family income (adjusted OR=2.16, 95%CI=1.13-4.14), good attitude towards a Pap test (OR=1.87, 95%CI=1.09-4.23), and having received a recommendation from health care providers were important factors associated with decisions to attend cervical cancer screening (OR=1.73, 95%CI=1.01-4.63). From in-depth interviews, there were five reasons of their decisions to attend cervical cancer screening including yearly check-up, postpartum check-up, having abnormal symptom, encouragement by health care providers, and request from workplace. CONCLUSIONS High family income, good attitude towards a Pap test, and receiving proper recommendation by health care providers, were important factors associated with decision to have cervical cancer screening among women 30-60 years old. Trying to enhance these factors and reduce barriers regarding screening, may increase the coverage rate for cervical cancer screening in Thailand.

Personalized Cancer Treatment for Ovarian Cancer

Recently there have been numerous advances in understanding the genetic basis of cancer which have resulted in more appropriate treatments. In this paper we describe the experience of the Burzynski Clinic, involved in treatment of numerous patients based on personalized approach using novel combinations for difficult-to-treat malignancies, with gynecological cancers. This retrospective study was conducted by extracting data from Burzynski Clinics medical records and comprehensive review. Among the advanced refractory ovarian cancers cases (N=33), an objective response (OR) was found in 42.4%. We anticipate that with improved technology and novel therapeutics this rate will increase and adverse events will be reduced.

Preventing cervical cancer: stakeholder attitudes toward CareHPV-focused screening programs in Roi-et Province, Thailand.

Objective: To assess which of the 5 CareHPV-inclusive protocols stakeholders in Roi-et Province, Thailand found (1) most preferable and (2) most beneficial to the overall goal of reducing cervical cancer. Design: Five CareHPV-inclusive cancer prevention approaches were presented to a convenience sample of colposcopists, trainers, health care providers, district medical directors, and district health officers. Participants ranked their preference for each plan (A-E) compared with the current screening protocol and also the perceived comparative benefit of the plans. Plans differed in whether every patient was screened using both the human papillomavirus (HPV) test and visual inspection with acetic acid (VIA) or only HPV-positive women were screened with VIA; in clinician versus self-swab and in hospital/clinic-based or village-based screening. Results: Overall, participants supported an innovative plan in which women would be screened in their homes and villages using the self-swab version of the CareHPV DNA test, and only those who screened positive for HPV are screened with VIA. When results were stratified by provider type (physician vs nonphysician) and/or practice concentration (hospital-oriented vs field-oriented), preference and perceived benefit for the plans differed significantly with physician/hospital-oriented participants and are more likely to be skeptical of the self-swab version of the CareHPV test. Conclusions: Providers in Thailand recognize the potential value of a rapid HPV test as part of a cervical cancer prevention program and, overall, support a patient-administered self-swab followed by visual confirmation and treatment as the most practical CareHPV-inclusive approach largely because of the likely increase in coverage. Future studies will further define the clinical benefits and limitations of this test.