Hepatitis C virus seroprevalence in the general female population from 8 countries.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant global health issue because it is widespread and persistent and can cause serious liver diseases. OBJECTIVES: The aim of this study is to estimate HCV prevalence in women from the general population in different geographical areas worldwide and to assess the potential role of sexual behaviour in the virus transmission. STUDY DESIGN: Each participating centre recruited a random sample of women from the general population aged from less than 20 to more than 75 years. The study included 8130 women from 8 countries with information on sociodemographic factors, reproductive and sexual behaviour, smoking habit and HPV DNA through individual interviews. A blood sample was also collected to perform serological tests. We estimated the prevalence ratios associated to HCV to evaluate the effect of sexual behaviour in viral transmission. RESULTS: Women were reactive to a minimum of two HCV antigens, including at least one non structural protein were considered as positive (33% of the samples were classified as positive, 40% as negative, and 27% as indeterminate (N=402), that were considered as not positive). The age-adjusted HCV seroprevalence varied significantly by regions (0.3% in Argentina to 21.1% in Nigeria). We found no association between HCV prevalence and age, educational level, smoking habit and any of the available variables for sexual behaviour and reproductive history. CONCLUSIONS: This large study showed heterogeneous distribution of HCV seroprevalence in female and provides evidence of the null impact of sexual behaviour in HCV transmission.

Cytomorphologic and clinical factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) smears.

OBJECTIVE: To determine the predictors for high-grade cervical intraepithelial neoplasia (CIN)/invasive carcinoma in women with atypical squamous cells, cannot exclude the high-grade squamous intraepithelial lesion (ASC-H) smears. MATERIAL AND METHOD: All women with ASC-H, who underwent colposcopy and had histolopathologic diagnosis between January 2004 and December 2011, were recruited. Clinical and cytomorphologic features were correlated with final histological diagnosis. Univariate and multivariate analysis were used to determine predicting factors for high-grade CIN/ invasive cancer RESULTS: Among 136,638 smears performed, 193 (0.14%) smears were reported as ASC-H and 121 smears were available for review. The underlying pathology were negative/reactive (N/R) 57 (47.1%), CIN 1 23 (19.0%), CIN 2-3 39 (32.0%), and invasive cancer 2 (1.6%). On univariate analysis, predicting factors of having high-grade CIN included a high N/C ratio, greater nuclear hyperchromasia, nuclear membrane irregularities, and the coarse chromatin. The multivariate analysis showed that a high nuclear-to-cytoplasmic (N/C) ratio (OR = 8.6, 95% CI = 1.1-70.1) and greater nuclear hyperchromasia (OR = 5.8, 95% CI = 1.6-20.8) were the independent predictors for high-grade CIN or invasive carcinoma. CONCLUSION: The presence of a high N/C ratio and greater nuclear hyperchromasia could be used to predict high-grade CIN or invasive carcinoma in ASC-H smears.

Economic evaluation of policy options for prevention and control of cervical cancer in Thailand.

BACKGROUND: The Thai healthcare setting has seen patients with cervical cancer experience an increasing burden of morbidity and mortality, a stagnation in the performance of cervical screening programmes and the introduction of a vaccine for the prevention of human papillomavirus (HPV) infection. OBJECTIVE: This study aims to identify the optimum mix of interventions that are cost effective, from societal and healthcare provider perspectives, for the prevention and control of cervical cancer. METHODS: A computer-based Markov model of the natural history of cervical cancer was used to simulate an age-stratified cohort of women in Thailand. The strategy comparators, including both control and prevention programmes, were (i) conventional cytology screening (Pap smears); (ii) screening by visual inspection with acetic acid (VIA); and (iii) HPV-16, -18 vaccination. Input parameters (e.g. age-specific incidence of HPV infection, progression and regression of the infection, test performance of screening methods and efficacy of vaccine) were synthesized from a systematic review and meta-analysis. Costs (year 2007 values) and outcomes were evaluated separately, and compared for each combination. The screening strategies were started from the age of 30-40 years and repeated at 5- and 10-year intervals. In addition, HPV vaccines were introduced at age 15-60 years. RESULTS: All of the screening strategies showed certain benefits due to a decreased number of women developing cervical cancer versus 'no intervention'. Moreover, the most cost-effective strategy from the societal perspective was the combination of VIA and sequential Pap smear (i.e., VIA every 5 years for women aged 30-45 years, followed by Pap smear every 5 years for women aged 50-60 years). This strategy was dominant, with a QALY gain of 0.01 and a total cost saving of Baht (Bt) 800, compared with doing nothing. From the societal perspective, universal HPV vaccination for girls aged 15 years without screening resulted in a QALY gain of 0.06 at an additional cost of Bt 8,800, based on the cost of Bt 15,000 for a full immunization schedule. The incremental cost-effectiveness ratio, comparing HPV vaccinations for girls aged 15 years with the current national policy of Pap smears for women aged 35-60 years every 5 years, was approximately Bt 18,1000 per QALY gained. This figure was relatively high for the Thai setting. CONCLUSIONS: The results suggest that controlling cervical cancer by increasing the numbers of women accepting the VIA and Pap smear screening as routine and by improving the performance of the existing screening programmes is the most cost-effective policy option in Thailand.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Correlation of p53 and Ki-67 (MIB-1) expressions with clinicopathological features and prognosis of early stage cervical squamous cell carcinomas.

AIM: To evaluate the prognostic significance of the expression of p53 and Ki-67, and their correlation with various clinicopathological factors in patients with squamous cell carcinoma of the uterine cervix treated by radical hysterectomy. METHODS: Two hundred and thirty five patients diagnosed between 1987 and 2004 were investigated for p53 and Ki-67 expression by immunohistochemistry. The relationship of these proteins and other potential prognostic factors with recurrence-free survival (RFS) was evaluated. RESULTS: The mean age of the patients was 43.9 years (range, 27-68). There were 28 cases with stage IA2 (11.9%) and 207 cases with stage IB1 (88.1%). The overall 5-year RFS was 91.1% (95% confidence interval [CI] 86.0, 94.4). p53 and Ki-67 expressions were seen in 33.6% and 81.3% of cases, respectively. p53 expression was significantly associated only with parametrial or marginal involvement (P = 0.005), while Ki-67 expression significantly correlated only with larger tumor (P = 0.011) and parametrial or marginal involvement (P = 0.024). There was significant correlation between the expression of p53 and Ki-67 (P = 0.021). In multivariate analysis, Ki-67 expression (hazard ratio for >or=3rd vs 1st tertile [>or=30% vs <20% expression] = 16.0, 95%CI 2.1-124.5; P = 0.0015) appeared to be an independent prognostic factor for RFS, while no prognostic significance of p53 expression was found. CONCLUSION: Ki-67 expression is an independent prognostic parameter for RFS in patients with early stage squamous cell carcinoma of the uterine cervix. Ki-67 expression at or above the cut-off point of 30.0% had significantly poorer RFS.

Type-specific seroprevalence of herpes simplex virus type 2 and associated risk factors in middle-aged women from 6 countries: the IARC multicentric study.

GOAL: To determine type-specific seroprevalence of herpes simplex viruses (HSV-1 and HSV-2) and HSV-2 risk factors. STUDY DESIGN: Six-hundred fifty eight middle-aged control women (hospital-based in 4 of 6 countries) from a multicenter cervical cancer case-control study participated from 1985 to 1997. Type-specific serum IgG antibodies against HSV-1 and HSV-2 were detected with Western Blot. RESULTS: HSV-1 seroprevalence was 89% to 100% everywhere except Thailand (51%). HSV-2 seroprevalence ranged from 9% (Spain) to 57% (Colombia), and was independently associated with having >or=2 lifetime sexual partners overall [Odds ratio (OR), 2.1; 95% confidence interval (CI) 2.5-3.1], and in Morocco (OR, 2.7; 95% CI, 1.2-6.1) and Thailand (OR, 4.4; 95% CI, 1.3-15.4), and with being unmarried in Colombia, Peru, Spain, but not significantly in Mali. Women whose male partner's sexual debut was

Lack of effect of perioperative blood transfusion during radical hysterectomy with lymph node dissection on the prognosis of cervical cancer stage Ib.

The aim of this retrospective study was to analyze the effects of perioperative blood transfusion during radical hysterectomy with lymph node dissection on the prognosis of cervical cancer stage Ib. A total of 295 patients who had undergone surgery from 1987-2002 were included. Forty seven patients underwent conization before definite surgery, and 2 patients were subsequently lost to follow up. Among the remaining 246 patients, 97 received allogenic blood transfusion, 38 received autologous blood transfusion, and 111 received no transfusion. The clinicopathologic finding of these three groups were reviewed and analyzed. There was no significant difference among three groups in age, chief complaints, duration of symptoms, size of lesion, histopathology, grade, margin or parametrium involvement, node status or postoperative adjuvant treatment. The most prominent presenting symptoms were abnormal vaginal discharge, abnormal vaginal bleeding, and postcoital bleeding. Although the 5-year disease-free survival (DFS) (and 95% CI) for autologous blood transfused group was 90.9% (74.4-97.0%), falling to 88.1% (77.8-93.8%) in untransfused blood group and 81.7% (71.3-88.6%) in allogenic transfused blood group, there were no significant differences among three groups (P = 0.699). In multivariate analyses, only age (P = 0.046), size of lesion (P = 0.024) and histology (P = 0.046) were statistically significantly associated with DFS, whereas transfusion status was not. In conclusion, there is no evidence that perioperative blood transfusion affects DFS of patients undergoing radical hysterectomy and pelvic lymphadenectomy. Only age, size of lesion and histology were statistically significantly associated with DFS.

Situation analysis for management of abnormal Pap smears in the lower southern Thailand.

OBJECTIVE: To identify the resources for management of abnormal Pap smears and the treatment facilities in pre-invasive cervical neoplasia in the lower southern Thailand. METHODS: After reviewing the necessary data, an expert meeting was scheduled for questionnaire development. The questionnaires were then sent to the general, regional, and university hospitals in the lower southern Thailand for self-evaluation and on-site visits were made for intensive interviews, exploring the services and treatment facilities for women with abnormal Pap smears. RESULTS: All of the 12 target hospitals provided passive cervical cancer screening although the quality of cytological services was obscure and the process of patient notification for the results of the abnormal Pap smears was not convincing. There was a limitation in the pathological laboratory services. The incidence of the abnormal Pap smears in the one-year period of the study, defined as atypical squamous cells of undetermined significance (ASCUS) or above and high grade squamous intraepithelial lesions (HSIL) or above were 1.24% (95% CI 1.15-1.32) and 0.36% (95% CI 0.30-0.43) respectively. All but one hospital reported having a colposcope, but only one could provide standard colposcopy services. The efficiency of the referral system is questionable. CONCLUSION: The resources for the management of abnormal Pap smears as well as the conventional referral system need to be reorganized. The data from this survey support the concept of a centralized colposcopy service with the University hospital as suitable place for the referral center. Two further 2 hospitals have potential for future development as referral centers.

Diagnostic evaluation of Karman endometrial aspiration in patients with abnormal uterine bleeding.

AIM: To assess sensitivity and specificity of Karman aspiration in the diagnosis of abnormal endometrium compared with the final diagnosis and evaluate tissue adequacy obtained by Karman aspiration. METHODS: The study group were women who presented with abnormal uterine bleeding to Songklanagarind Hospital between August 2003 and July 2004 and who underwent Karman aspiration prior to conventional curettage. The final diagnosis was defined as the most severe histopathology from either Karman aspiration or conventional curettage. Abnormal endometrium included inflammation, polyp, hyperplasia and malignant changes. RESULTS: Two hundred and twenty-six women were assessed. Endometrial aspiration showed a sensitivity of 89.6% and specificity 100.0% in diagnosis of abnormal endometrium. Abnormal endometrium was detected in 58 women. Of 11 women diagnosed with endometrial cancer, only one case was undetected by Karman aspiration due to a failure to create negative pressure in the uterus. Endometrial aspiration yielded adequate tissue in 86.7%. CONCLUSION: Karman endometrial aspiration is an accurate and easy procedure, and should be considered in the initial evaluation of abnormal uterine bleeding.

Clinico-pathological profile of vulva cancer in southern Thailand: analysis of 66 cases.

OBJECTIVE: To evaluate the clinico-pathologic findings and treatment outcome of women with vulva cancer in Southern Thailand. MATERIAL AND METHOD: The authors retrospectively reviewed the medical records of 66 women who had been treated with surgery from June 1984 to October 2003 at the Department of Obstetrics and Gynecology, Prince of Songkla University. RESULTS: The patients' age ranged from 30 to 87 years, mean 58.2 years. Two most common presentations were vulva mass (89.4%) and pruritus (57.6%). Duration of symptoms at presentation ranged form 1 month to 5 years. Most cases were squamous cell carcinoma (82.0%). The distribution by FIGO surgical stage I, II, III and IV was 9.1%, 47.0%, 34.8% and 9.1%, respectively. The most common complication was wound infection (45.5%), followed by wound dehiscence, lymphosis and leg edema (each 15.2%). The 5-year survival (and 95% CI) for stages I, II, III and IV was 100%, 96% (76-99%), 94% (63-99%) and 60 (13-88%), respectively. The 5-year survival for node-positive cases was 82% (54-94%) versus 100% for node-negative cases (p = 0.0003). Stage was a significant predictor of survival (p = 0.0142) and disease-free survival (p = 0.0112). CONCLUSION: Stage and nodal involvement are predictors of survival, and stage is a predictor of disease-free survival.

Management of pre-invasive cervical cancer in low-resource setting.

Cervical cancer is one of the health burdens in many developing countries. The advanced knowledge in the past decade reassured the important role of human papillomavirus as the necessary cause of cervical cancer and makes a clear understanding of its natural history. Cervical cancer has a long period of pre-invasive stage, and only a small proportion of cervical intraepithelial neoplasia (CIN) that can progress to be an invasive lesion. Appropriate management of CIN can prevent invasive cervical cancer. The contemporary treatment of CIN is more conservative and requires effective follow-up process. However inappropriate management of CIN is still be found at the international and national survey of less developed countries. Although no apparent superior surgical technique for treating CIN, loop electrosurgical excision procedure (LEEP) and cryotherapy are fascinated for the low-resource setting. Other alternative approach, which eliminates cytology and colposcopy may be considered in the ultrashort- resource setting with a high prevalence of cervical cancer. In this article, the contemporary knowledge about the natural history of cervical cancer, especially the implication of human papillomavirus (HPV) for pre-invasive cervical cancer, is summarized. The current approaches for treatment of CIN are reviewed from the perspective of low-resource settings. The various strategies for management approaches are demonstrated, and the cost-effectiveness is discussed. The pattern of pre-invasive cervical cancer management in developing countries, including in the south of Thailand is exhibited, and the single-visit service for cervical cancer prevention in the northeast is challenged.

Compliance with hormone replacement therapy at Songklanagarind Hospital.

AIM: To determine compliance with hormone replacement therapy (HRT) over a 2-year period, reasons for discontinuing HRT and the factors associated with non-compliance. METHODS: A total of 202 women attending the menopause clinic at Songklanagarind Hospital and taking HRT were included in this retrospective study. Compliance was assessed for each 6-month interval within the first 2 years. Reasons for discontinuation were requested from women who had stopped using HRT. RESULTS: Compliance rates with HRT for the study group were 57.9% at 6 months, 42.6% at 12 months, 35.1% at 18 months and 32.7% at 24 months. The main reasons for discontinuing HRT were improvement of climacteric symptoms (20.9%), fear of cancer (16.4%) and irregular bleeding (11.9%). Logistic regression analysis revealed a significant increase in the risk of non-compliance of HRT among agriculturists or untrained workers (OR 4.7, 95% CI 1.2-18.8; reference, government employees), those with delayed onset of treatment (>1 years; OR 3.0, 95% CI 1.1-8.0; reference, 0-3 months) and those prescribed HRT for climacteric symptoms or reasons other than oophorectomy or ovarian failure (OR 18.2-41.6 depending on reasons). Agriculturists or untrained workers who delayed onset of treatment for climacteric symptoms had the highest expected non-compliance rate of 0.95%. CONCLUSION: Long-term compliance of HRT was not good at Songklanagarind menopause clinic. More attention has to be paid to the counseling of patients about HRT. Agricultural or untrained workers, late starting HRT, and presence of climacteric complaints were the significant factors for poor HRT compliance.

Correlation of risk categorization in gestational trophoblastic tumor between old and new combined staging and scoring system.

AIM: To determine the correlation of risk categorization in gestational trophoblastic tumor between the revised International Federation of Gynecology and Obstetrics (FIGO) staging system combined with the original World Health Organization (WHO) scoring system, and the new FIGO staging system combined with the modified WHO scoring system. METHODS: We reviewed the medical records of 124 patients with gestational trophoblastic disease seen at Songklanagarind Hospital from 1988 to 2000. All patients were classified retrospectively by the FIGO staging system (both the revised system in 1992 and the new system in 2000) and the WHO scoring system (both the original and the modified one). The correlation of risk categorization between the revised FIGO staging system combined with the original WHO scoring system (old combined system), and the new FIGO staging system combined with the modified WHO scoring system (new combined system) was studied, and the remission rates in discrepant groups were identified. RESULTS: The mean score was 9.7+/-5.0 (range 1-21) for the original WHO and 8.3+/-5.0 (range 1-20) for the modified WHO. The correlation of risk categorization between old and new combined systems was 97.9%. There was no patient in the low risk group as classified by the old combined system, but patients were classified as in the high risk group by the new combined system. One patient, who was in the high risk group classified by the old combined system, but in the low risk group classified by the new combined system, achieved complete remission after treatment with single agent chemotherapy. CONCLUSION: There was good correlation between the old and the new combined systems.

Population-based human papillomavirus prevalence in Lampang and Songkla, Thailand.

To investigate the prevalence and determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer, we studied 1741 women >/=15 years of age from Lampang and Songkla, Thailand. Exfoliated cervical cells were collected for Papanicolaou smear screening and DNA detection of 36 different HPV types. Serum immunoglobulin G antibodies against L1 virus-like particles (anti-VLPs) of HPV-16, -18, -31, -33, and -58 were evaluated using enzyme-linked immunosorbent assay. Overall, 110 women (6.3%) were HPV DNA positive; the most common types were HPV-16, -52, and -72. The age-standardized prevalence of HPV DNA was higher among the 1035 women from Lampang (9.1%; 95% confidence interval [CI], 7.1-11.1) than among the 706 women from Songkla (3.9%; 95% CI, 2.3%-5.6%). Anti-VLPs were found in 21.8% of all women and were more frequent among women from Lampang (29.2%) than among women from Songkla (10.9%). Major risk factors for cervical HPV DNA were age <35 years, HSV-2 seropositivity, and having a husband with extramarital sexual partners.

Situation analysis of atypical squamous cells of undetermined significance smears in Songklanagarind Hospital.

OBJECTIVE: To review the incidence, management, follow-up rate and colposcopic diagnosis of atypical squamous cells of undetermined significance (ASCUS) detected on cervical smears in Songklanagarind Hospital, Thailand. METHODS: A retrospective study of ASCUS smears taken during January 2000 to March 2001 at Songklanagarind Hospital was performed. The type of management was classified and the follow-up rate was detected. Cases with colposcopy, tissue biopsy, endocervical curettage, conization and hysterectomy specimen were reviewed. In the cases without tissue biopsy, the final diagnoses were based on the colposcopic examination. RESULTS: Among the 25068 Pap smears examined, the incidence of ASCUS was 0.62%. Of these, only 56.13% received the further evaluation. The non-compliance rate was 18.71%. The incidences of cervical intraepithelial neoplasia (CIN) and invasive cancer among the cases who received colposcopy were 15.96% and 2.13%, respectively. The incidence of CIN or invasive cancer in ASCUS favor reactive and ASCUS favor neoplasia were not different statistically significant. CONCLUSIONS: Management of ASCUS smears by follow-up may be inappropriate. A practice guideline which consists of active management, intensive follow-up system and well-organized data management should be used to improve the situation.

Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners.

BACKGROUND: It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. METHODS: We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). RESULTS: Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. CONCLUSIONS: Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.