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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

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.

Background Cervical 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. Methods HPV 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. Results Overall, 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. Conclusion The 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. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0886-z) contains supplementary material, which is available to authorized users.

The p16INK4a protein is immunocytochemically detected in liquid-based (LB) specimens as a diagnostic marker of cervical dysplasia and neoplasia. Its up-regulation is promoted by high-risk human papillomavirus (HR-HPV) infection. We aimed to detect p16INK4a on conventional Papanicolaou (Pap) test (CPT) slides and to determine the relationship between its overexpression and HR-HPV infection. CPT and LB Pap test (LBPT) slides (165 samples of each) were examined by immunocytochemical staining for p16INK4a. After polymerase chain reaction (PCR), HPV-DNA was genotyped by dot blot hybridization. The CPT slides displayed more numerous dispersed squamous cells and LBPT slides had a clearer background. Positive p16INK4a on CPT occurred in 0% (0/30), 52.5% (21/40), 54.3% (19/35), 100% (30/30), and 100% (30/30) in normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs), high-grade SILs (HSILs), and squamous cell carcinomas (SCCs) cases, respectively. LBPT slides showed comparable results but were less sensitive. HPV-DNA was detected in 86.7, 70, 45, 57.14, and 10% in SCCs, HSILs, ASCUS, LSILs, and normal cervical cells, respectively. Because HR-HPV was identified in all HPV+ samples of high-grade dysplasia (HSILs and SCCs) and all positive p16INK4a samples infected with HR-HPV, the association of p16INK4a overexpression with HR-HPV infection was confirmed. This study suggests that immunocytochemical staining of p16INK4a on CPT slides is convenient and cost-effective for cervical cancer screening by the detection of dysplastic cells infected with HR-HPV.

OBJECTIVE: To develop an immunocytochemical technique for p16 INK4a protein detection in scraped cervical cells for cancer screening. STUDY DESIGN: We took duplicate cervical scrapes from each participant, the first for a Pap smear and the second for p16 INK4a protein detection. From a 50-pL cell suspension prepared from the scrape rinsing, a 10-μL aliquot was dropped in a 5-film-diattieter circle on a glass slide, air dried and fixed in 0.1% formal saline (1 hour) and in 95% ethanol (10 minutes). Using the immunocytochemical technique, slides from 30 samples of each Pap diagnosis class were stained sequentially with mouse monoclonal anti-p16 INK4a (primary antibody), biotinylated goat antimouse IgG (secondary antibody), horseradish peroxidase-labelled streptavidin and 3,3'-diaminobenzidine and mixed hydrogen peroxide, then counterstained with hematoxylin. A positive sample had to contain ≥ 3 immunoreactive cells. Results were confirmed by western blot analysis of lysates from the remaining 40 μL of each cervical cell suspension. RESULTS: Samples were grouped as control (normal cervical cells), mild dysplasia (ASCUS, LSIL) and high abnormality (HSIL, SCC). Using the immunocytochemical technique, > 95% of the positive (SiHa cells) but 0% of the negative controls (human embryonic lung fibroblast cells) shouted immunoreactive cells. All slides displayed a clear background without mucus, and positive cells were stained in both the cytoplasm and nucleus. p16 INK4a Protein was detected in 17 of 30 (56.67%) ASCUS and 10 of 30 (33.33%) LSIL and increased with the degree of abnormality to 93.33% (28 of 30) and 96.67% (29 of 30) in the HSIL and SCC group, respectively. Normal cervical cells and degenerated malignant cells were nonimmunoreactive. Western blot analysis confirmed similar positive samples in the low-abnormality group, while the whole high-abnormality group was immunoreactive. A sampling error might have caused the 2 HSIL and 1 SCC sample to be negative using our immunocytochemical technique. CONCLUSION: p16 INK4a Protein detection in scraped cervical cells using the immunocytochemical technique correlated with western blot analysis and was nontraumatic and precise. It offers a significant diagnostic adjunct to the Pap test for cervical cancer screening.

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

Thailand is in the process of developing a national cervical screening program. This study examined p16INK4a staining and HPV prevalence in abnormal cervical samples with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL), to evaluate the efficacy of combined HPV and p16INK4a detection to predict CIN II-III. Totals of 125 ASCUS and 87 LSIL cases were re-evaluated by Pap test and cervical cells of ASCUS and LSIL cases were prepared on slides for p16INK4a detection by immunocytochemistry. HPV genotyping of DNA extracts was performed by GP5+/6+ PCR and reverse line blot hybridization. Histopathologic tests were performed to identify cervical lesion. Total of 212 cases were diagnosed to normal (20), ASCUS (112), LSIL (78) and HSIL (2). HPV was detected in ASCUS (49/112, 43.8%), LSIL (60/78, 76.9%) and HSIL (2/2, 100%) cases. The majority of HPV positive samples typed for high-risk HPV. 55.7% (107/192) of abnormal cases (ASCUS, LSIL and HSIL) were positive p16INK4a. For the 111 HPV DNA positive cases, 34 of 49 (69.4%) ASCUS cases and 49 of 60 (81.7%) LSIL cases were p16INK4a positive. 140 biopsies were taken and histological classified: CIN negative (65 cases), CIN I (56 cases) and CIN II-III (19 cases). HPV DNA detection predicted CIN II-III with sensitivity and specificity of 84% and 49%, whereas p16INK4a staining showed higher sensitivity (89.5%) and specificity (56.2%). The prediction of CIN II-III was significantly better by combination of positive HPV DNA and p16INK4a with 93.8% sensitivity and 59.2% specificity. Detection of HPV DNA combined with p16INK4a in cervical cells can predict CIN II-III and may improve the screening diagnosis of Thai women at risk for CIN II-III or cancer.

To identify risk factors other than high risk human papillomavirus infection for the development of cervical cancer, functional polymorphisms of DNA repair genes, XRCC1 Arg399Gln and Arg194Trp and XRCC3 Thr241Met, were studied among Northeastern Thai women. Cases (n=111) were defined as squamous cell cervical cancer and controls (n=118) were recruited from healthy women without cervical abnormalities. The XRCC1 194Trp/Trp genotype significantly increased the risk for cervical cancer (OR=5.52; 95%CI=1.14-26.64; p=0.03). Among the HPV infection negative group, significantly higher risks for cervical cancer were visualized for XRCC1 399Arg/Gln (adjusted OR=3.69; 95%CI=1.04-13.06; p=0.04) and XRCC1 194Arg/Trp (adjusted OR=4.13; 95%CI=1.13-15.12; p=0.03). This study indicates that variant types of DNA repair genes play partial roles in modifying individual susceptibility to cervical cancer. Since cervical cancer is a multi-factorial disease, the contribution of DNA repair enzymes to the development of cervical cancer, if it exists may be concealed by HPV infection.

To evaluate treatment response and acute treatment-related toxicity of concurrent chemoradiotherapy with cisplatin 20 mg/m2 , compared to 40 mg/m2 as the standard, in locally advanced cervical cancer.A prospective randomized controlled trial in Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen.140 patients,60 years old with biopsy-proven previously untreated invasive carcinoma of cervix, FIGO stage IB2-IVA, undergoing concurrent chemoradiotherapy with adequate bone marrow, renal and liver functions, between April and December 2009.All patients were randomly assigned (half in each group)to receive weekly cisplatin at a dose of 40 mg/m2 compared to 20 mg/m2, concurrent with radiotherapy for 6 cycles. Main outcome measures included clinical response, cytological response, and acute treatment-related toxicity.All 140 patients completed 6 cycles of weekly cisplatin. 80% had squamous cell carcinomas; about half were FIGO stage IIIB. The 40 mg/m2 group showed unplanned interruptions in 13/70 (18.6%), which was significantly different from the 5/70 (7.1%) in the 20 mg/m2 group (p=0.02), resulting in prolonged treatment time (p=0.026). Complete responses were found in 69/70 (98.6%) and 68/70 (97.1%), respectively, with no significant difference. Hematological and gastrointestinal toxicities were most frequently observed. Acute toxicities in the first group was significantly higher when compared to the second group (p0.05) as follows; grade 1-2 leukopenia (14.8% vs. 6.4%), grade 1-2 neutropenia (9.3% vs. 2.6%), grade 2 N/V (3.8% vs. 1%), grade 2 diarrhea (2.4% vs. 0.7%), and grade 1 sensory neuropathy (4.5% vs. 1.2%). No treatment related deaths were encountered.This prospective trial has sufficient data to support the conclusion that concurrent chemoradiotherapy with weekly cisplatin 40 mg/m2 in locally advanced cervical cancer gives good treatment outcomes. When reducing the cisplatin dose to 20 mg/m2, treatment responses were still comparable to the standard, but acute toxicity could be reduced. However, there are insufficient data to assess long term treatment outcomes and late treatment related toxicity, because of the short follow-up time.

To evaluate the relationships between genetic polymorphisms of the GSTs (GSTM1 and GSTT1) and cervical cancer, the null genotype of each gene was studied in squamous cell cervical cancer (SCCA) patients (n=90) and controls (n=94) in Northeast Thailand. The prevalence of the GSTM1-null genotype in the controls and SCCA patients was 59.6% and 60.0%, respectively, whereas those of the GSTT1-null genotype in the control and SCCA patients was 40.4% and 46.7%, respectively. Neither of the GST-null genotypes increased the risk for SCCA (p0.05); however, the combination of the GSTM-1 and GSTT1-null genotypes showed a non-significant trend for an increased risk for developing cervical cancer with an adjusted OR of 2.7 (95%CI=0.8-9.0, p=0.10). Genetic polymorphisms of GSTM1 and GSTT1 were not significant risk factors for cervical cancer in either tobacco-smokers or non-smokers. A different contribution of the GST genotype to cancer risk may be attributed to a different, as yet undefined, property of the enzymes.

High risk human papillomaviruses (HR-HPVs) are associated with increased risk of normal cervical cells developing to dysplasia and cervical carcinoma. Therefore, HR-HPV DNA testing can predict an endpoint of cervical carcinogenesis that is earlier than the development of cervical abnormalities. Not only the sensitivity of methods but also the amount of HPV DNA are very important and might be parameters to distinguish HPV detection. In this study, we evaluated the effects of primer sets and the polymerase chain reaction (PCR) performance with low viral load samples with normal cervical cytology (140 samples) and mild dysplasia (140 samples) using two consensus primers MY09/MY11 and GP5+/6+. The PCR was performed with single and nested PCR. Positive samples with both primer sets were then HPV genotyped by dot blot hybridization. Results showed higher sensitivity of single PCR using primer GP5+/GP6+ than primer MY09/MY11. HPV DNA was detected in 15% (21 of 140)and 20.7% (29 of 140) of normal cervical samples, respectively. For mild dysplasia samples, HPV DNA was detected in 37.1% (52 of 140) with MY09/MY11 and 50% (70 of 140) using GP5+/GP6+. In normal cervical samples, the positivity rate was increased to 38.5% (54 of 140) by nested PCR using primer GP5+/6+, but only 2 mild dysplasia samples that were negative by single GP5+/6+ were positive by auto-nested PCR. These results suggested that, in low viral load samples, the sensitivity of HPV DNA detection depends not only on primer sets but also PCR performance. HPV 16 was the most common in mild dysplasia samples (20.8%), whereas HPV type 58 was found in 11.1%. This study suggested that nested PCR might be necessary for HPV DNA detection in cervical samples of women participating in cervical cancer screening.

As part of an ongoing project involving a large cohort in the Khon Kaen Province in the North-east of Thailand, a total of 236 women who had tested positive for a Pap smear at the initial recruitment and advised to seek medical attention were followed up after a mean period of 3.1 years. The 204 individuals who could be contacted were interviewed to determine treatments received and underwent a further Pap smear as well as colposcopy in 179 of the cases. On clinical advice, biopsies were also taken from 32 of these. Only 15% of the total of 204 had actually received therapy, the majority undergoing surgery (self-reported). Possible positive Pap smear results were obtained for 23.5%, with 6.4% having high grade squamous intraepithelial lesions (HGSILs) or squamous cell carcinoma (SCC) (one case). Comparison of the different testing modalities demonstrated 5.6% false negatives and 16.2 false positives for the Pap smear with colposcopy as the gold standard. Compared with biopsy findings, there were 21.8% and 40.6% false positives with Pap and colposcopy, respectively, but no false negatives. The present results point to good efficacy for the initial screening, since only 0.5% of the total population developed an SCC. However, judgement as to therapy should depend on a biopsy since there were considerable false positives with the other two modalities employed.

The aim of this study was to evaluate the compliance, response, and side effects of weekly gemcitabine (125 mg/m(2)) given concomitantly with standard weekly cisplatin (40 mg/m(2)) and pelvic radiotherapy for primary treatment of cervical cancer stage IB2-IVA in the first seven Thai cases.Weekly gemcitabine at a dose of 125 mg/m(2) was given concomitantly with cisplatin at 40 mg/m(2) 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.Using weekly gemcitabine at a dose of 125 mg/m(2) with cisplatin at a dose of 40 mg/m(2), 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.Weekly gemcitabine at a dose of 125 mg/m(2) with cisplatin at a dose of 40 mg/m(2) 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/m(2).

This study aimed to investigate the histological outcome of cervix with human papillomavirus (HPV) infection and the association of risk factors with cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) development in Northeast Thai women. The study population (n=210) comprised 71 cases of normal cervix, 71 cases of CIN and 68 cases of ICC. The histological outcome of HPV infection was determined for 9.5% of the study population. Increased risk factors for CIN were observed for more than one partner (odds ratio (OR)=3.75, p0.05), history of sexually transmitted disease (STD) (OR=2.28, p0.05), menarche under 14 years of age (OR=0.31, p0.05) and partners' smoking history (OR=3.98, p0.01). Increased risk for ICC was observed for those with a history of STDs (OR=0.14, p0.01) and multiparity (OR=2.53, p0.01). Age at first sexual intercourse was not a risk factor in this study population. Further studies with HPV-DNA tests should more precisely quantify the risks.

Risk factors for cervical squamous intraepithelial lesions (SIL) including human papillomavirus (HPV) infection and the p53 codon 72 polymorphism were investigated in a case-control study with 103 cases and 105 controls in Northeastern Thailand. Increased risk for SIL was observed for age at menarche (odds ratio (OR) = 2.2; p0.005), age at the first sexual intercourse (OR=2.4; p0.05), number of sexual partners (OR=2.7; p0.005) and partners' smoking history (OR=2.3-3.2; p0.01). Prevalence of malignant type of HPV infection in the control and SIL groups was 18.1% and 60.2%, respectively. HPV infection significantly increased risk for SIL 6.8-fold (p0.001). HPV-16 infection was the commonest (31 out of 62 carriers) in SIL patients and highly associated with risk. The p53 codon 72 polymorphism was not identified as a genetic risk for SIL in this study, as demonstrated in Thai cervical cancer. Therefore, to prevent cervical neoplasia or HPV infection, inclusion of knowledge on sexual behavior and effects of smoking into public health programs is important and, at the same time, a nation-wide screening scheme for cervical abnormalities including HPV-typing is a high priority in Thailand.

The purpose of this study was to determine the incidence of the loss of heterozygosity (LOH) among normal cervixes, cervical intraepithelial neoplasias (CINs) and invasive cervical cancers (ICCs). DNA samples (136) were obtained from 31 normal cervixes, 49 CINs and 56 ICCs. Four polymorphic microsatellite markers (D3S1300, D3S1351, D3S1478 and D3S4103) covering the chromosome 3p arm, were employed. LOH at one or more loci were identified in: 9/31 (8.1%) normal cervixes, 17/49 (14.6%) CINs and 26/56 (22.1%) invasive cancers. The incidence of the LOH at 3p varied for each locus and ranged from 5.6% for D3S1351 to the highest rate of 16.6% for D3S1300. We thus found that LOH of chromosome 3p can occur in normal cervixes and that incidences increase in CINs and ICCs. Deletion in the 3p14.2 (D3S1300) and 3p21.2 (D3S1478) regions might be an early event and, in fact, necessary for cervical cancer progression. The loss of function of tumor suppressor genes (TSGs) located in these regions may have a sequential effect in cervical cancer carcinogenesis.

HPV infection is the main cause of cervical cancer; however, factors that promote and maintain HPV infection are still unclear. This study was designed to search for factors responsible for the HPV infection in Northeastern Thai women. A total of 190 volunteers with a normal histopathologic appearance of cervix as controls (n=100) and with squamous cell cervical carcinoma (SCCA) (n=90) were the subjects. Variables of risk factors including sexual behaviors, history of reproduction, history of sexually transmitted diseases and smoking were conducted with self-report and direct interview. Number of sexual partners and smoking history increased the likelihood of high-risk HPV infection. Multiple sexual partners showed significantly higher 3.94-fold risk for HPV infection (95% CI = 1.82-8.82, p-value0.001). Smoking history of partner increased the risk for HPV infection 3.03-fold (95%CI=1.42-6.58, p-value0.002). After OR were adjusted, significant difference was still observed in the number of sexual partners (p-value0.0001) and smoking history of the partner (p-value0.005). To decrease the incidence of cervical cancer, we should prevent HPV dissemination and be on the alert for having multiple sexual partners and a partner's smoking habit, which must be included in our public health planning.

Relationships between cervical cancer and risk factors were investigated in Northeastern Thailand. Cases (n = 90) with squamous cell cervical cancer (SCCA) and age matched healthy controls (n = 100) were recruited. The p53 codon 72 polymorphism, proline and arginine allele, was studied by the polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference in the allele and the genotype distribution between the SCCA and the control groups (P > 0.05). Significant difference was observed in the number of sexual partners (P < 0.003) age at the first sexual intercourse (P < 0.03) and number of parities ( P< 0.006). After adjusted by age and p53 genotype, significant difference was still observed in the number of sexual partners (P = 0.017) The partners' smoking increased the risk to develop SCCA. Increased odds ratios were observed when the partner had smoking history both at present (3.31; P < 0.003) and in the past (3.36; P < 0.003). The p53 polymorphism itself may not be a risk factor for cervical cancer in Northeastern Thailand. Much attention should be paid to the presence of other risk factors such as sexual behaviors and smoking habits in the prevention of cervical cancer in this region.

Background We aimed to determine (i) if other sexually transmitted infections (STIs) increase the risk of incident human papillomavirus (HPV) infection and (ii) if HPV infection predicts the incidence of other STIs. Methods Women aged 20–38 years were followed semi-annually for 18 months in Thailand (n=1200). Assessment was made on cervical HPV genotypes, cervical cytology, sexual behaviour, demographic factors and diagnoses of other STIs including chlamydia, gonorrhoea, syphilis, genital herpes and trichomoniasis. Incident detection was defined as any type-specific HPV or other STI which was detected at current visit but not at previous visit. Associations were measured by ORs with 95% CIs estimated in generalised estimating equation models. Results During follow-up, 241 new cases of HPV, 110 incident cases of high risk (HR)-HPV and 46 new cases of other STIs were observed. Diagnosis of other STIs at previous visit was statistically significantly associated with twofold increased odds of any new HPV detection after controlling for sexual behaviour, age, pap smear status and contraceptive use [adjusted OR (aOR): any HPV: 2.16 (95% CI: 1.08% to 4.34%)] (Abstract O1-S02.02 table 1). No significant association was found between diagnosis of other STIs and subsequent incident detection of HR-HPV [aOR: 2.01 (95% CI: 0.74% to 5.48%)] (Abstract O1-S02.02 table 1). Positive detection of any HPV or HR-HPV predicted nearly twofold increased odds of other STIs with the estimates bordering on statistical significance [aORs: any HPV: 1.81 (95% CI: 0.94% to 3.49%); HR-HPV: 2.00 (95% CI: 0.82% to 4.83%)] (Abstract O1-S02.02 table 2). Conclusions We show that other STIs increase the risk of HPV incidence after controlling for sexual behaviour. The data qualitatively suggest mutual associations of HPV with other STIs. Further studies are warranted to evaluate if these reflect true biologic interactions between HPV and other sexually transmitted microbial agents, or mere confounding from unmeasured sexual risks.

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. 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.

Objective We sought to investigate CpG-island methylation profiling of apoptotic genes apoptotic protease activating factor 1, caspase 8, death-associated protein kinase (DAPK), tumor necrosis factor receptor superfamily member 6 (FAS), Survivin, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and its role in resistance to therapy in cervical cancer (CXCA). Study Design Methylation status was performed in 85 CXCA patients comprising therapeutic nonresponses and responses using methylation-specific polymerase chain reaction. Results Methylation frequency of DAPK and FAS showed a statistically significant difference between therapeutic nonresponses and responses. Concurrent methylation of multiple apoptotic genes was a preferential event in CXCA. Moreover, concerted methylation of pair genes was observed in DAPK, FAS, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and found only in nonresponses. Conclusion Aberrant methylation of apoptotic signaling genes results in acquired resistance to therapy. Detection of methylation in apoptotic signaling genes is potentially useful as a molecular predictive marker for strategic planning of treatment efficacy and evaluation of therapeutic outcome in CXCA, leading to an improvement of patients' survival.