Pissamai Yuenyao

The use of viral load as a surrogate marker in predicting disease progression for patients with early invasive cervical cancer with integrated human papillomavirus type 16.

OBJECTIVE The purpose of this study was to assess the effectiveness of the use of human papillomavirus type 16 (HPV16) physical status and viral load in combination to predict clinical outcome during cervical development. STUDY DESIGN A follow-up study was monitored in association with HPV integration and viral load in 121 cervical samples with the use of multiplex quantitative polymerase chain reaction. RESULTS A significant increase of viral load was found earlier from preinvasive to invasive groups compared with normal groups, except with clinical staging and clinical outcome. High occurrence of integrated HPV16 was observed in preinvasive (27/44 samples) and invasive cervical carcinoma (40/68 samples). Cervical progression was observed significantly in most preinvasive (18/27 samples) and invasive cases (25/40 samples) that were infected with integrated HPV. Integrated HPV16 with significant viral load can be used as a predictive marker for tumor progression in the early stage of invasive cervical carcinoma. CONCLUSION Integrated HPV16 in combination with viral load is a predictive indicator for tumor progression in early invasive stage but not in preinvasive and advanced invasive stage.

Human Papillomavirus Genotypes and Cervical Cancer in Northeast Thailand

Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

Risk factors for cervical cancer in northeastern Thailand: detailed analyses of sexual and smoking behavior.

Cervical cancer is a serious public health problem in Thailand. We investigated possible risk factors for cervical cancer including HPV infection, p53 polymorphism, smoking and reproductive history among women in Northeast Thailand using a case control study with 177 cases and age-matched controls. Among the HPV carriers, a significantly increased risk for cervical cancer with an OR of 36.97 (p<0.001) and an adjusted OR of 38.07 (p<0.001) were observed. Early age at first sexual exposure, and multiple sexual partners increased the risk of cervical cancer with ORs ranging between 1.73-2.78 (p<0.05). The interval between menarche and first sexual intercourse<6 years resulted in a significant increase in the risk for cervical cancer with ORs ranging between 3.32-4.09 and the respective adjusted OR range for the 4-5 and 2-3 year-old groups were 4.09 and 2.92. A higher risk was observed among subjects whose partner had smoking habits, whether currently or formerly; with respective ORs of 3.36 (p<0.001) and 2.17 (p<0.05); and respective adjusted ORs of 2.90 (p<0.05) and 3.55 (p<0.05). Other smoking characteristics of the partners including smoking duration≥20 years, number of cigarettes smokes≥20 pack-years and exposure time of the subject to passive smoking≥5 hrs per day were found to be statistically significant risks for cervical cancer with adjusted ORs of 3.75, 4.04 and 11.8, respectively. Our data suggest that the risk of cervical cancer in Thai women is substantially associated with smoking characteristics of the partner(s), the interval between menarche and first sexual intercourse as well as some other aspects of sexual behavior.

The association of hormonal contraceptive use and HPV prevalence.

Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long‐term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV‐negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high‐risk (HR)‐HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR‐HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long‐term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin‐only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection.

Prevalence and correlates of HPV among women attending family-planning clinics in Thailand

BackgroundCervical cancer is the most common cancer among women of reproductive age in Thailand. However, information on the prevalence and correlates of anogenital HPV infection in Thailand is sparse.MethodsHPV genotype information, reproductive factors, sexual behavior, other STI and clinical information, and cervical cytology and histology were assessed at enrollment among one thousand two hundred and fifty-six (n = 1,256) HIV negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. The type-specific prevalence of HPV was estimated using cervical swab specimens from healthy women and women with a diagnosis of CIN 2/3 at baseline. Prevalence ratios (95% CI) were estimated using Poisson regression to quantify the association of demographic, behavioral, and clinical correlates with prevalent HPV infection.ResultsOverall, 307 (24.6%) and 175 (14.0%) of women were positive for any HPV type and any HR-HPV type, respectively; the most common types were 72, 52, 62, and 16. Among women diagnosed with CIN 2/3 at enrollment (n = 11), the most prevalent HPV types were 52 and 16. In multivariate analysis, HPV prevalence at enrollment was higher among women with: long-term combined oral contraceptive use, a higher number of lifetime sexual partners, a prior Chlamydia infection, and a current diagnosis of Bacterial Vaginosis.ConclusionThe study findings provide important information that can be used in the evaluation of primary and secondary interventions designed to reduce the burden of cervical cancer in Thailand.

Kinetics of DNA load predict HPV 16 viral clearance

INTRODUCTION While high HPV 16 viral load measured at a single time point is associated with cervical disease outcomes, few studies have assessed changes in HPV 16 viral load on viral clearance. OBJECTIVE To measure the association between changes in HPV 16 viral load and viral clearance in a cohort of Thai women infected with HPV 16. STUDY DESIGN Fifty women (n=50) between the ages of 18-35 years enrolled in a prospective cohort study were followed up every three months for two years. Women positive for HPV 16 DNA by multiplex TaqMan assay at two or more study visits were selected for viral load quantitation using a type-specific TaqMan based real-time PCR assay. The strength of the association of change in viral load between two visits and viral clearance at the subsequent visit was assessed using a GEE model for binary outcomes. RESULTS At study entry, HPV 16 viral load did not vary by infection outcome. A >2 log decline in viral load across two study visits was found to be strongly associated with viral clearance (AOR: 5.5, 95% CI: 1.4-21.3). HPV 16 viral load measured at a single time point was not associated with viral clearance. CONCLUSIONS These results demonstrate that repeated measurement of HPV 16 viral load may be a useful predictor in determining the outcome of early endpoints of viral infection.

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

PurposeThe aim of this study was to evaluate the compliance, response, and side effects of weekly gemcitabine (125 mg/m2) given concomitantly with standard weekly cisplatin (40 mg/m2) and pelvic radiotherapy for primary treatment of cervical cancer stage IB2–IVA in the first seven Thai cases.Materials and methodsWeekly gemcitabine at a dose of 125 mg/m2 was given concomitantly with cisplatin at 40 mg/m2 for six cycles with concurrent radiotherapy in primary therapy of stage IB2–IVA cervical cancer. Radiation consisted of 5000 cGy in 25 daily fractions combined with brachytherapy to take point A to about 8600 cGy.ResultsUsing weekly gemcitabine at a dose of 125 mg/m2 with cisplatin at a dose of 40 mg/m2, five of seven patients demonstrated a dose-limiting toxicity (DLT). DLTs consisted of nephrotoxicity in three cases and bone marrow suppression in two cases. Only one of seven patients could go through six cycles. All 5 living patients had a clinically complete response.ConclusionsWeekly gemcitabine at a dose of 125 mg/m2 with cisplatin at a dose of 40 mg/m2 given concurrently with primary pelvic radiotherapy resulted in an excellent response but unacceptable toxicities for Thai women. The trial protocol was changed by reducing the cisplatin dosage to 20 mg/m2.

Srinagarind Hospital experience in concurrent chemoradiation for 100 patients with stage IB2 to IVA uterine cervical cancer.

PurposeThe aim of this study was to determine responses, acute adverse effects, and survival outcomes of women with stage IB2 to IVA treated with weekly cisplatin concurrent with pelvic irradiation at Srinagarind Hospital.Materials and methodsThe medical records of 100 women with cervical cancer stage IB2 to IVA who were treated with weekly cisplatin 40 mg/m2 concurrent with pelvic radiotherapy at Srinagarind Hospital between January 2003 and June 2006 were reviewed and analyzed.ResultsDuring the study period, 100 women were eligible for analysis, with a mean age of 46 years (range 24–60 years). Distribution according to International Federation of Gynecology and Obstetrics (FIGO) staging was IB2 1.0%, IIB 47.0%, IIIB 51.0%, and IVA 1.0%, respectively. A total of 86 patients received five or more cycles of weekly cisplatin. Grade 3 and 4 hematologic toxicities were found in 6.0%. The overall response rate was 97.0%. Complete response was achieved in 86 patients (86.0%) and partial response in 11 patients (11.0%). Stable disease was found in 1 patient (1.0%) but no progressive disease was found. Progression-free survival and overall survival rate were 69.6% and 96.1%, respectively.ConclusionWeekly cisplatin (40 mg/m2) concurrent with pelvic irradiation for locally advanced cervical cancer was effective with acceptable toxicity in Thai women.

P1-S5.32 The differential associations of HPV prevalence with other sexually transmitted infections in hormonal and non-hormonal contraceptive users

Background This study evaluated the associations of recent sexually transmitted infections (STIs) with cervical HPV prevalence among hormonal and non-hormonal contraceptive users. Methods Data came from a prospective study conducted in 1046 women aged 20–38 years with normal cervical cytology in Thailand. We assessed whether baseline HPV prevalence was predicted by STIs which were newly detected and laboratory-confirmed within 2 years prior to enrolment. Prevalence ratios (PRs) with 95% CIs were estimated using generalised linear models. Results Baseline prevalence of any HPV and high-risk (HR)-HPV were 19.9% and 8.7% respectively. Having genital chlamydia (CT) or gonorrhoea (NG) in the past 2 years was associated with increased risk of any HPV as well as HR-HPV infection after controlling for current and past sexual behaviours, age, contraceptive use and other concurrent STIs [adjusted PRs (aPRs) for any HPV: CT: 1.7 (95% CI 1.1 to 2.7), NG: 1.8 (95% CI 1.1 to 3.1); aPRs for HR-HPV: CT: 2.9 (95% CI 1.3 to 6.5); NG: 3.4 (95% CI 1.7 to 6.7)]. Association between CT and prevalent HR-HPV was statistically significant only among non-hormonal contraceptive users [aPR: 2.7 (95% CI 1.2 to 6.3)] but not among those using hormonal contraceptives in the past 2 years [aPR: combined oral contraceptive (COC) users: 1.1 (95% CI 0.5 to 2.4); users of depot medroxyprogesterone acetate (DMPA): 1.1 (95% CI 0.4 to 3.3)] (Abstract P1-S5.32 table 1). Association of NG with prevalent HR-HPV was observed among those who used COC [aPR: 6.2 (95% CI 2.2 to 17.7)] or DMPA [aPR: 3.5 (95% CI 1.1 to 10.9)] during the past 2 years but not among non-hormonal contraceptive users [aPR: 1.9 (95% CI 0.3 to 10.3)] (Abstract P1-S5.32 table 1). No significant association was found between other STIs and baseline prevalence of HR-HPV in this cohort. Abstract P1-S5.32 Table 1 Association between recent genital infections and prevalent detection of high-risk HPV (N=1046) Total study population a Study population stratified by use of contraceptives in the past 2 years* Detection of any HR-HPV Detection of any HR-HPV Non-hormonal contraceptive users (n=339) COC users (n= 294) DMPA users (n= 413) N = 1046, N (col %) HR-HPV+ n=91 (8.7%), n (row %) PR (95% CI) aPR‡ (95% CI) PR (95% CI) aPR§ (95% CI) PR (95% CI) aPR§ (95% CI) PR (95% CI) aPR§ (95% CI) Detection of the following in the past 2 years† Genital chlamydia  No 925 (88.4) 72 (7.8) 1 1 1 1 1 1 1 1  Yes 121 (11.6) 19 (15.7) 2.02 (1.26 to 3.22) 2.93 (1.33 to 6.47) 3.73 (1.69 to 8.26) 2.74 (1.18 to 6.34) 1.70 (0.84 to 3.47) 1.14 (0.54 to 2.39) 1.22 (0.44 to 3.35) 1.08 (0.35 to 3.28) Genital gonorrhea  No 1020 (97.5) 84 (8.2) 1 1 1 1 1 1 1 1  Yes 26 (2.5) 7 (26.9) 3.27 (1.68 to 6.36) 3.40 (1.73 to 6.65) 2.31 (0.37 to 14.46) 1.87 (0.34 to 10.29) 4.24 (1.79 to 10.03) 6.22 (2.18 to 17.73) 3.29 (1.13 to 9.60) 3.51 (1.13 to 10.93) Bacterial vaginosis  No 875 (83.7) 74 (8.5) 1 1 1 1 1 1 1 1  Yes 171 (16.4) 17 (9.9) 1.18 (0.71 to 1.94) 1.05 (0.63 to 1.75) 1.03 (0.40 to 2.66) 0.75 (0.31 to 1.82) 1.04 (0.46 to 2.36) 0.90 (0.40 to 2.03) 1.57 (0.66 to 3.68) 1.46 (0.57 to 3.70) Positive for HSV-2 serology  No 626 (59.9) 47 (7.5) 1 1 1 1 1 1 1 1  Yes 420 (40.2) 44 (10.5) 1.40 (0.94 to 2.07) 1.26 (0.83 to 1.91) 1.99 (0.90 to 4.38) 1.75 (0.78 to 3.90) 1.53 (0.84 to 2.80) 1.67 (0.89 to 3.15) 0.88 (0.41 to 1.88) 0.73 (0.30 to 1.79) The following covariates were not found to be statistically significantly associated with the outcomes (P>0.05) and did not significantly influence the effect size of the primary association of interest (<10%), and hence were not included in the final models: parity, smoking status, as well as other parameters assessed for sexual behavior, including age of sexual debut, having new partner in the past year, number of sex partners in the past year, frequency of sex in last 6 months. HR-HPV: High-risk HPV, defined as HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 (IARC 2007). * Subjects were formerly enrolled in a 2-year study addressing the effects of hormonal contraceptive use on HIV acquisition (HC-HIV). These subjects were required to adhere to the self-selected contraceptive method for at least 1 year of follow-up in that study (Morrisonet al. AIDS. 2010;24:1778–81). These subjects were reconsented at the end of that study for inclusion in the current study. † Genital infections were detected in pelvic exams and confirmed by laboratory assays. ‡ Estimates adjusted for age at baseline of the current study, number of lifetime partners, partners having sex with others in last 6 months, male partner using condom in last 6 months, other concurrent genital infections, types of contraceptive use in the past 2 years. § Estimates adjusted for age at enrollment of the current study, number of lifetime partners, partners having sex with others in last 6 months, male partner using condom in last 6 months, other concurrent genital infections. COC, combined oral contraceptives; DMPA, depot medroxyprogesterone acetate; HSV-2, Herpes simplex virus 2; PR, Prevalence ratio. Conclusions The differential impact of recent hormonal contraceptive use on the associations of CT and NG with HR-HPV prevalence suggests that the observed correlations may be attributed to biologic interactions between the pathologies of HPV and CT or NG, and not merely residual confounding by shared sexual risks.