Objective: This study assessed whether sexual behavior, including engaging in early sexual intercourse and having had multiple sexual partners, can predict the risk of infection with cervical human papillomavirus (HPV) types 16 and 18. Methods: Records were reviewed of women who underwent cervical cancer screening and were found to be infected with high-risk HPV. The genotypes of high-risk HPV were categorized as HPV 16, HPV 18, and other than 16 or 18. Early sexual intercourse was defined as first sexual intercourse at the age of 19 years or younger. Multiple sexual partners was defined as having more than three lifetime sexual partners. Associations between sexual behavior and HPV 16/18 infection were presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of the 349 women included in the study, 72 (20.6%) and 30 (8.6%) were infected by HPV 16 and 18, respectively. Eighty-two women (26.0%) reported having engaged in early sexual intercourse, and 33 (10.4%) reported having had multiple sexual partners. After adjustment for age, parity, and smoking habits, we found that women who had engaged in early sexual intercourse tended to have a higher risk of HPV 16 (OR 1.74; 95% CI 0.93–3.29), and those who had had multiple sexual partners were found to be at a significantly higher risk for HPV 18 (OR 4.58; 95% CI 1.44–14.58). Conclusion: Sexual behavior was associated with an increased risk of HPV 16/18 infection. Engaging in early sexual intercourse increased the risk of HPV 16 infection, and having had multiple sexual partners increased that of HPV 18.
Background: The variation of human papillomavirus (HPV) genes or HPV variants demonstrates different risks of cervical cancer. Mutation in the long control region (LCR) at YY1-motifs is one of the mechanisms for enhancing viral oncogene expression during the course of cancer cell progression. In Thai women, cervical cancers are almost always associated with HPV16 variant sub-lineage Asian (HPV16As); however, the mechanism involved remains elusive. The aim of this study was to understand further the oncogenic potential of HPV16As. Methods: A total of 82 HPV16-positive specimens from Thai women were selected from formalin-fixed paraffin-embedded cervical tissues, and the full length E6 gene of each specimen was amplified and sequenced. LCRs of the HPV16As-positive cases were amplified and sequenced to analyze their polymorphisms. Transcriptional activities of the HPV16As LCRs were then compared with sub-lineage European (EUR), sub-lineage Asian-American 1 (AA1) and HPV16 prototype by insertion of the LCRs into the pGL3-Basic vector. Results: The HPV16 DNA sequences were classified as HPV16 prototype (18.3%), Asian (As, 61%), Asian American-1 (AA1, 8.5%), European (EUR, 7.3%), Asian African-2 (AFR2, 3.7%) and Java-135C (J135C, 1.2%). The prevalence of HPV16As was 30% in low-grade squamous intraepithelial lesion (LSIL), while that in high-grade squamous intraepithelial lesion (HSIL) and squamous cell cervical carcinoma (SCC) were 63.9% and 66.7%, respectively, which demonstrates a significant association of HPV16As with the disease severity. LCR polymorphisms from 43 HPV16As positive cases were analyzed by PCR-sequencing. Thirty-eight nucleotide variation positions spanned nucleotide positions 7157–82. Ten new mutations found in the HPV16As LCRs were located predominantly at the enhancer and proximal to the 3’-end of the early promoter. The LCRs of the common HPV16As, EUR and AA1 showed 5, 13 and 23-fold higher activity than the HPV16 prototype LCR, while those of the new nucleotide variations of As showed 19 (As-sv1) and 30 (As-sv14) -fold higher activity than the HPV16 prototype. Conclusions: HPV16As DNA sequence variation, especially at the proximal to early promoter in the LCR, enhances transcriptional activity. This could be one of the possible mechanisms for HPV16As-associated cervical cancer development.
Incidence and risk factors for insufficient endometrial tissue from endometrial sampling Apiwat Aue-aungkul, Pilaiwan Kleebkaow, Chumnan Kietpeerakool Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Objective: To assess the incidence of and factors that predict insufficient tissue after endometrial sampling. Methods: This study reviewed the records of women undergoing endometrial sampling at Khon Kaen University’s Srinagarind Hospital between June 2014 and June 2015. It excluded cases in which the device could not be inserted into the uterine cavity due to pain intolerance or equipment failure. The criterion for diagnosing insufficient endometrial tissue was a lack of any intact tissue fragments containing both glands and stroma. Results: Medical records of 233 women were reviewed. Insufficient tissue following endometrial sampling was noted in 67 cases (28.8%; 95% confidence interval [CI]=23.0–35.0). Histologic results in the remaining 166 women included normal pathological endometrium (121, 51.9%), endometrial polyps (7, 3.0%) endometrial hyperplasia (27, 11.6%), and endometrial cancer (11, 4.7%). According to multivariable analysis, menopausal status (odds ratio [OR] =3.60, 95% CI=1.84–7.05) and endometrial thickness of less than 8 mm (OR=3.91, 95% CI=1.49–10.21) were significant independent predictors for insufficient endometrial tissue after endometrial sampling. Conclusion: The incidence of insufficient tissue following endometrial sampling was 28.8%. Significant independent factors associated with an increased risk of insufficient tissue were menopausal status and endometrial thickness of less than 8 mm. Keywords: insufficient endometrial tissue, endometrial sampling, Endocell®, sample adequacy, inadequate sampling
The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data. Therefore, this study aimed to develop MM–based scores for predicting the risk of precancerous cervical lesion progression and identifying precancerous lesions in patients in northern Thailand by evaluating the expression of multiple biomarkers. The MMs (Models 1–5) were developed in the test sample set based on patient age range (five categories) and biomarker levels (cortactin, p16INK4A, and Ki–67 by immunohistochemistry [IHC], and HPV E6/E7 ribonucleic acid (RNA) by in situ hybridization [ISH]). The risk scores for the prediction of cervical lesion progression (“risk biomolecules”) ranged from 2.56–2.60 in the normal and low–grade squamous intraepithelial lesion (LSIL) cases and from 3.54–3.62 in cases where precancerous lesions were predicted to progress. In Model 4, 23/86 (26.7%) normal and LSIL cases had biomolecule levels that suggested a risk of progression, while 5/86 (5.8%) cases were identified as precancerous lesions. Additionally, histologic grading with a single molecular biomarker did not identify 23 cases with risk, preventing close patient monitoring. These results suggest that biomarker level–based risk scores are useful for predicting the risk of cervical lesion progression and identifying precancerous lesion development. This multiple biomarker–based strategy may ultimately have utility for predicting cancer progression in other contexts.
1 March 2019 in Asian Pacific Journal of Cancer Prevention
Objectives: To evaluate prevalence of underlying significant pathologies among women with cervical smearsrated as ‘atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)’, as well asassociated risk factors. Methods: Medical records were reviewed of all consecutive women with ASC-H smears whohad undergone colposcopy at Srinagarind Hospital from January 2008 to July 2016. Significant pathology resultsincluded cervical intraepithelial neoplasia (CIN) 2-3, adenocarcinoma in situ (AIS), endometrial hyperplasia, andcancer of any original site. Result: During the study period, 133 women with ASC-H were reviewed. The mean agewas 45.3 years (range 21-72). The histopathologic results for the 133 women were as follows: no lesions (58; 43.6%),CIN 1 (34; 25.6%), CIN 2-3 (33; 24.8%), AIS (2; 1.5%), and cervical cancer (6; 4.5%). The overall rate of significantpathology was 30.8% (95% confidence interval, 22.9%-38.8%). Women younger than 40 years old carried a higherrisk of harboring significant lesions when compared to older women (41.7% versus 27.8%, respectively). There wasno significant impact of parity and menopausal status on the risk of significant pathology results. Conclusion: Therate of significant histopathologies among women with ASC-H smears in this study was approximately 31% and theassociated risk factor was patient age.