• Korean Journal of Community Nutrition
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• v.28 no.1
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• pp.61-73
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• 2023

Objectives: Prophylactic vaccines against high-risk human papillomaviruses (HR-HPVs) hold promise to prevent the development of higher grade cervical intraepithelial neoplasia (CIN 2+) and cervical cancer (CC) that develop due to HR-HPV genotypes that are included in HPV vaccines, but women will continue to develop CIN 2+ and CC due to HR-HPV genotypes that are not included in the quadrivalent HPV vaccine (qHPV) and 9-valent HPV vaccine (9VHPV). Thus, the current vaccines are likely to decrease but not entirely prevent the development of CIN 2+ or CC. The purpose of the study was to determine the prevalence and determinants of CIN 2+ that develop due to HR-HPVs not included in vaccines. Methods: Study population consisted of 1476 women tested for 37 HPVs and known to be negative for qHPVs (6/11/16/18, group A, n = 811) or 9VHPVs (6/11/16/18/31/33/45/52/58, group B, n = 331), but positive for other HR-HPVs. Regression models were used to determine the association between plasma concentrations of micronutrients, socio-demographic, lifestyle factors and risk of CIN 2+ due to HR-HPVs that are not included in vaccines. Results: The prevalence of infections with HPV 31, 33, 35 and 58 that contributed to CIN 2+ differed by race. In group A, African American (AA) women and current smokers were more likely to have CIN 2 (OR = 1.76, P = 0.032 and 1.79, P = 0.016, respectively) while in both groups of A and B, those with higher vitamin B12 were less likely to have similar lesions (OR = 0.62, P = 0.036 and 0.45, P = 0.035, respectively). Conclusions: We identified vitamin B12 status and smoking as independent modifiable factors and ethnicity as a factor that needs attention to reduce the risk of developing CIN 2+ in the post vaccination era. Continuation of tailored screening programs combined with non-vaccine-based approaches are needed to manage the residual risk of developing HPV-related CIN 2+ and CC in vaccinated women.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6093-6097
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• 2015

Background: HPV DNA testing has been recently introduced as an adjunct test to cytology in the follow-up of patients after treatment for cervical lesions using the loop electrosurgical excision procedure (LEEP). The aim of this study was to evaluate the role of HPV testing in the detection of persistent or recurrent disease after LEEP in patients with cervical epithelial lesions in northern Thailand. Materials and Methods: Patients who underwent LEEP as a treatment for histological low-grade (LSIL) or high-grade squamous intraepithelial lesion (HSIL) or worse at Chiang Mai University Hospital between June 2010 and May 2012 were included. Follow-ups were scheduled at 6-month intervals and continued for 2 years using co-testing (liquid-based cytology and Hybrid Capture 2 [HC2]) at 6 months and 24 months and liquid-based cytology alone at 12 and 18 months. Results: Of 98 patients included, the histological diagnoses for LEEP included LSIL in 16 patients, and HSIL or worse in 82 patients. The LEEP margin status was negative in 84 patients (85.7%). At follow-up, 10 patients (10.2%) had persistent/recurrent lesions; 4 among LSIL patients (25.0%) and 6 in the group with HSIL or worse (7.3%). Only 2 of 82 patients (2.4%) with HSIL or worse diagnoses had histological HSIL in the persistent/recurrent lesions. Using histologically confirmed LSIL as the threshold for the detection of persistent/recurrent disease, cytology had a higher sensitivity than HC2 (90.0% versus 70.0%). At the 6-month follow-up appointment, combined cytology and HC2 (co-testing) had a higher sensitivity in predicting persistent/recurrent disease (80.0%) compared with that of cytology alone (70.0%) and HC2 (50.0%). Conclusions: After LEEP with a negative surgical margin, the rate of persistent/recurrent lesions is low. The addition of HPV testing at the 6-month visit to the usual cytology schedule may be an effective approach in the follow-up after LEEP.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5867-5872
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• 2014

Background: Cervical cancer is listed as one of high-incidence endemic diseases in Xinjiang. Our study aimed to evaluate the expression of TLR9 in uterine cervical tissues of Uyghur women and examine associations with clinicopathological variables. We further characterized the direct effects of TLR9 upon the selective silencing of human papillomavirus (HPV) E6 and E7 oncoprotein expression in HPV 16-positive human cervical carcinoma cells treated with siRNA in vitro. Materials and Methods: Immunohistochemistry was applied to evaluate TLR9 expression in 97 formalin-fixed paraffin-embedded cervical samples from Uyghur women; 32 diagnosed with cervical squamous cell carcinomas (CSCC), 14 with low-grade cervical intraepithelial neoplasias (CINI), 10 medium-grade (CINII), 24 high-grade (CINIII), and 17 chronic cervicitis. $BLOCK-iT^{TM}$ U6 RNAi Entry Vector $pENTR^{TM}$/U6-E6 and E7 was constructed and transfected the entry clone directly into the mammalian cell line 293FT. Then the HPV 16-positive SiHa human cervical carcinoma cell line was infected with RNAi recombinant lentivirus. RT-PCR and Western blotting were used to determine the expression of TLR9 in both SiHa and HPV 16 E6 and E7 silenced SiHa cells. Results: Immunohistochemical staining showed that TLR9 expression was undetectable (88.2%) or weak (11.8%) in chronic cervicitis tissues. However, variable staining was observed in the basal layer of all normal endocervical glands. TLR9 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathological grade in the following order: chronic cervicitis (2/17, 11.8%)

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6837-6842
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• 2014

Background: Northern Thailand is a region with a high cervical cancer incidence. Combined high-risk HPV (hrHPV) DNA testing and cytology (co-testing) has increasingly gained acceptance for cervical cancer screening. However, to our knowledge, data from a population-based screening using co-testing have not been available in this region. This study therefore aimed to evaluate the performance of cytology and hrHPV test in women in northern Thailand. Materials and Methods: Cervical samples were collected for hybrid capture 2 (HC2) testing and liquid-based cytology from women aged 30 to 60 years who were residents in 3 prefectures of Chiang Mai in northern Thailand between May and September 2011. Women with positive cytology were referred to colposcopy, while women with positive for HC2 only were followed for 2 years. Results: Of 2,752 women included in this study, 3.0% were positive in both tests, 4.1% for HC2 only, and 1.3% had positive cytology only. At baseline screening, positive HC2 was observed in 70.6% among cytology-positive women compared with 4.3% among cytology-negative women. The prevalence of positive HC2 or cytology peaked in the age group 35-39 years and was lowest in the age group 55-60 years. High-grade squamous intraepithelial lesion or worse lesions (HSIL+) were histologically detected in 23.5% of women with positive baseline cytology and in 9.8% of women with positive baseline HC2 only on follow-up. All women with histologic HSIL+ had positive baseline HC2. Conclusions: The hrHPV test is superior to cytology in the early detection of high-grade cervical epithelial lesions. In this study, the prevalence of histologic HSIL+ on follow-up of women with positive hrHPV test was rather high, and these women should be kept under careful surveillance. In northern Thailand, hrHPV testing has a potential to be used as a primary screening test for cervical cancer with cytology applied as a triage test.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10961-10966
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• 2015

Background: Minor cervical cytologic abnormalities include atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of women with minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+). In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referral for colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ to reduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test in triage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All women with ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014 were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopic examination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results: There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantly higher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detected in 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was no histologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). The performance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in the cut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value. Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage of women with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off threshold for HC2 triage is not recommended in this region.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4163-4167
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• 2016

Background: Cervical cancer is the second most common in Thailand, but the mortality rate may be rising yearly. It is a cancer that can be prevented by early screening for precancerous lesions, several methods being available. Objective: To identify the prevalence of abnormal Papanicolaou (Pap) smears and lesions with visual inspection with acetic acid (VIA) in pregnant women and assess risk factors for this group. Materials and Methods: This prospective study was performed at Prapokklao Hospital, Thailand during April-July 2016. All pregnant women of gestational age between 12-36 weeks who attended an antenatal clinic were recruited. All participants were screened for cervical cancer by Pap smear and VIA. If results of one or both were abnormal, colposcopic examination was evaluated by gynecologic oncologist. Results: A total of 414 pregnant women were recruited. Prevalence of abnormal Pap smear and VIA were 6.0 and 6.7 percent, respectively. The most common abnormal Pap smear was low grade intraepithelial lesion (LSIL, 44%). Factors associated with abnormal Pap smear in pregnant women were low BMI, multiple partners and being a government officer. In pregnancy, Pap smear had higher sensitivity and specificity than VIA for detection of precancerous cervical lesion. Patients with young coitarche or more than 25 years of active sexual activity were high risk groups. Conclusions: Prevalence of abnormal Pap smear and VIA in pregnant women was 6.0 and 6.7 percent, respectively. Factors associated with abnormal Pap smear were coitarche, years of sexual activity, low BMI, multiple partners and being a government officer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2073-2080
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• 2015

Background: The human papillomavirus (HPV) and its variants show wide geographical distribution and have been reported to cause cervical lesions. With cervical neoplasia as the leading cancer in Indian women, the aim of the present study was to evaluate the multiple infection HPV type distribution and variant genotypes in cervical samples from the coastal Karnataka region, India. Materials and Methods: A total of 212 samples were screened by nested polymerase chain reaction using PGMY9/11 and GP5+/6+ primers. HPV positive samples were sequenced to identify the types and a phylogenetic tree was constructed using the neighbor-joining method. Results: Sequence analysis identified a total of 14 HPV types distributed in 20%, 73.3% and 82.5% of non-malignant, pre-malignant [low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in cancer samples was HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35, 1.4% and HPV 45, 1.4%. Multiple infections were observed in 11.8% of tumor samples with HPV 16 contributing to 62.5% of cases. In non-malignant samples, 20% of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58, 5.8% and very low incidence of multiple infections. Comparative phylogenetic analysis of HPV variants identified 9 HPV sequences as new papillomavirus species, predominantly classified as European lineage type. Conclusions: The findings for HPV infections associated with progression of cervical cancer in coastal Karnataka region and HPV variant analysis provide baseline data for prevention and HPV vaccination programs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6693-6696
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• 2013

Background: Cold knife conization is a surgical procedure that allows both diagnosis and treatment of cervical lesions at the same time. It is mainly performed for indications of high-grade cervical intraepithelial neoplasia (CIN). In this study, we aimed to investigate the clinical outcome of cases without CIN in cold knife conization specimen, following a high-grade lesion (CIN2/3) in cervical biopsy. Materials and Methods: We performed a retrospective cohort study at a tertiary referral hospital between January $1^{st}$ 2008 and August $1^{st}$ 2012. Cases that underwent cold knife conization for CIN2/3 within the study period were included. Cone-negative (Group 1) and cone-positive (Group 2) cases were analyzed for various clinical parameters, and were compared in the 1-year post-conization period for histological recurrence and human papillomavirus (HPV) DNA status. Results: A total of 173 women underwent cold knife conization for CIN2/3 within the study period. Twenty-two cases (12.7%) were included in Group 1 and 151 cases (87.3%) in Group 2. There were no significant differences between the two groups in terms of age, gravidity, parity, menopausal status and HPV-DNA status (pre-conization and 1 year post-conization) (p>0.05). Recurrence rates were also similar between the groups (9.1% vs 9.9%, p>0.05). Conclusions: Clinical outcomes were similar in terms of histological recurrence and HPV persistence after 1 year of follow-up between cone-negative and cone-positive cases. Clinical follow-up of cone-negative cases should therefore be performed similar to cone-positive cases.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.111-118
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• 2008

Background : Cervicovaginal cytology is a screening test of uterine cervical cancer. The sensitivity of cervicovaginal cytology is less than 50%, but studies of cytologic/histologic correlation are limited. We analyzed the diagnostic accuracy of cervicovaginal cytology in the detection of the squamous epithelial lesions of the uterine cervix and investigate the cause of diagnostic discordance. Materials and Methods : We collected a total of 481 sets of cervicovaginal cytology and biopsies over 5 years. The cytologic diagnoses were categorized based on The Bethesda System and the histologic diagnoses were classified as negative, flat condyloma, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, or squamous cell carcinoma. Cytohistologic discrepancies were reviewed. Results: The concordance rate between the cytological and the histological diagnosis was 79.0%. The sensitivity and specificity of cervicovaginal cytology were 80.6% and 92.6%, respectively. Its positive predictive value and negative predictive value were 93.7% and 77.7%, respectively. The false negative rate was 19.4%. Among 54 false negative cytology cases, they were confirmed by histology as 50 flat condylomas, 2 CIN I, 1 CIN III, and 1 squamous cell carcinoma. The causes of false negative cytology were sampling errors in 75.6% and interpretation errors in 24.4%. The false positive rate was 7.4%. Among 15 false positive cytology cases, they were confirmed by histology as 12 atypical squamous cells of undetermined significance (ASCUS) and 3 low grade squamous intraepithelial lesions (LSIL). The cause of error was interpretation error in all cases. The overall diagnostic accuracy of cervicovaginal cytology was 85.7%. Conclusions : Cervicovaginal cytology shows high overall diagnostic accuracy and is a useful primary screen of uterine cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5001-5004
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• 2015

The Reid colposcopic index (RCI) helps physicians for interpret the results of colposcopic examination. To compare the accuracy of RCI in colposcopic evaluation between general and oncologic gynecologists, this prospective trial was conducted by invited women over 20 years of age who were scheduled for a colposcopy at Chiang Mai University Hospital between August, 2008 and May, 2014 to participate. Pregnant patients or those having a history of hysterectomy or conization were excluded. During the colposcopy, all patients were simultaneously evaluated by general and oncologic gynecologists utilizing the RCI. Further management with either a biopsy or LEEP in each patient was dependent on the decision of the attending oncologic gynecologist. The accuracy of the RCI in diagnosing HSIL or more was calculated by the comparison with the final histology. Finally, 135 patients were recruited into this study. The sensitivity, specificity, PPV, NPV, and accuracy of RCI in diagnosing HSIL or more in general gynecologists were 45.2%, 80.7%, 41.1%, 83.2% and 72.6% while in the oncologic gynecologists were 51.6%, 85.6%, 51.6%, 85.6% and 77.8%, respectively. The difference in accuracy between evaluator groups was not significant (p-value=0.28). Of 3 patients with invasive cervical cancer, all were undetected by the general gynecologists using RCI while only 1 invasive cervical cancer was missed via RCI by the oncologic gynecologists. We conclude that RCI could be used by general gynecologists in provincial hospitals with major concerns about missing invasive cervical cancer. A short training period regarding colposcopy might help to resolve this problem.