Long-Term Survival and Clinicopathological Implications of DNA Mismatch Repair Status in Endometrioid Endometrial Cancers in Hong Kong Chinese Women.

To investigate the role of DNA mismatch repair status (MMR) in survival of endometrioid endometrial cancer in Hong Kong Chinese women and its correlation to clinical prognostic factors, 238 patients with endometrioid endometrial cancer were included. Tumor MMR status was evaluated by immunohistochemistry. Clinical characteristics and survival were determined. Association of MMR with survival and clinicopathological parameters were assessed. MMR deficiency (dMMR) was found in 43 cases (16.5%). dMMR was associated with poor prognostic factors including older age, higher stage, higher grade, larger tumor size and more radiotherapy usage. Long-term survival was worse in dMMR compared to the MMR proficient group. The dMMR group had more deaths, shorter disease-specific survival (DSS), shorter disease-free survival (DFS), less 10-year DSS, less 10-year DFS, and more recurrence. The 5-year DSS and 5-year DFS in the dMMR group only showed a trend of worse survival but did not reach statistical significance. In conclusion, dMMR is present in a significant number of endometrioid endometrial cancers patients and is associated with poorer clinicopathological factors and survival parameters in the long run. dMMR should be considered in the risk stratification of endometrial cancer to guide adjuvant therapy and individualisation for longer follow up plan.

Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth.

Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/ß, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.

Paclitaxel Induces Immunogenic Cell Death in Ovarian Cancer via TLR4/IKK2/SNARE-Dependent Exocytosis.

Emerging evidence shows that the efficacy of chemotherapeutic drugs is reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated damage-associated molecular patterns (DAMP, such as CALR exposure, ATP secretion, and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which led to the activation of NF-κB-mediated CCL2 transcription and IkappaB kinase 2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced endoplasmic reticulum stress, which triggered protein kinase R-like ER kinase activation and eukaryotic translation initiation factor 2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T-cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer.

Prevalence and impact of hepatitis B virus infection in ovarian cancer patients in an endemic area-A retrospective cohort study.

Hepatitis B virus (HBV) infection is associated with many extrahepatic malignancies, but its association with and impact on ovarian cancer has not been examined. We therefore examined the prevalence of HBV infection among women with primary ovarian carcinoma in an endemic area, and whether this impacts the presentation and survival of these patients. In a retrospective study, we reviewed 523 patients presenting with primary ovarian cancer and known HBV status between 1 January 2006 and 31 December 2017. Patients were divided into HBV-positive and negative groups for the comparison of the patient characteristics and presentation, including staging and histological types, and short term (2 years) mortality from ovarian cancer. Among the 10.1% (53/523) patients screened positive for HBV, more of them presented with advanced staging at FIGO stage 3 or above (OR 1.378, 95% CI 1.063-1.787), although there were no significant differences in patient characteristics. Within 24 months from presentation, there were more deaths due to malignancy in the HBV-positive group (73.3% vs 44.2%, OR 1.659, 95% CI 1.135-2.425). On multivariate analysis after adjusting for nulliparity status, previous use of oestrogens, presence of metastases, histological type (epithelial or others) and grading (high grade or not), whether optimal debulking was performed, and chemotherapy, HBV infection was independently associated with increased death within 24 months of presentation (aOR 2.683, 95% CI 1.015-7.091). In conclusion, the findings of this study suggested an adverse effect of chronic HBV infection on survival within two years of presentation in patients with primary ovarian cancer.

Liquid biopsy of HPV DNA in cervical cancer.

BACKGROUND: A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. OBJECTIVES: To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. STUDY DESIGN: Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. RESULTS: The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 µL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. CONCLUSIONS: HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

Liquid biopsy of PIK3CA mutations in cervical cancer in Hong Kong Chinese women.

INTRODUCTION: Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. RESULTS: PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). CONCLUSIONS: As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.

Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients.

We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients' plasma: 60-64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.

We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer.

Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm.

MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.

Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus.

INTRODUCTION: Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence. METHODS: Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA. RESULTS: For subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells. CONCLUSIONS: In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response.

Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China.

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.

Debulking metastatic pelvic nodes before radiotherapy in cervical cancer patients: a long-term follow-up result.

BACKGROUND: Enlarged pelvic nodes are commonly found during preoperative imaging studies in cervical cancer patients and may represent tumor metastasis. It remains controversial whether debulking of these enlarged nodes prior to definitive radiotherapy offers any survival benefit to the patient. METHODS: Enlarged suspicious pelvic nodes identified by imaging studies in stage 1B to stage IIA (early-stage) cervical cancer patients prior to scheduled radical hysterectomy and in stage 1B2 or above (advanced-stage) cervical cancer patients destined for radiotherapy were debulked. Patients with confirmed nodal metastasis (node-positive) were primarily treated by radiotherapy and patients with no evidence of nodal metastasis (node-negative) were treated as planned. Clinical outcomes of these two groups of patients are reported after a long-term follow-up. RESULTS: Sixteen of 110 early-stage and 37 of 97 advanced-stage cervical cancer patients had their enlarged metastatic nodes removed before they were treated by radiotherapy. Microscopic metastatic pelvic nodes were found in six additional patients after the radical hysterectomy and four of them received postoperative adjuvant radiotherapy. After a median follow-up of 62 months, the rates of recurrence inside the pelvis are not significantly different between node-positive and node-negative patients with both early-stage and advanced-stage disease. Recurrences outside the pelvis occurred in 59.1% early-stage and 44.8% advanced-stage node-positive patients, and were the primary cause of poor survival. CONCLUSIONS: Debulking enlarged metastatic pelvic nodes may help reducing pelvic recurrence but does not seem to benefit survival.

Clinical use of laparoscopic ultrasonography in detecting nodal metastasis in advanced-stage cervical carcinoma.

OBJECTIVE: To assess the clinical use of a laparoscopic ultrasound scan (LUS) to identify pelvic and para-aortic node metastasis in patients with advanced-stage cervical cancer. METHODS: After examination under general anesthesia and cystoscopy, LUS was used to examine the pelvic nodes of patients with advanced-stage cervical cancer. Abnormal nodes were excised before definitive treatment to confirm the nodal status. Patients without abnormal para-aortic nodes on preoperative computer tomography/magnetic resonance imaging in the past 3 years were surgically staged via laparoscopic extraperitoneal aortic node sampling, and the findings were correlated with LUS findings. The predictive values of abnormal pelvic nodes on LUS for pelvic and aortic node metastasis were determined. RESULTS: A total of 119 advanced-stage cervical cancer patients underwent LUS of pelvic nodes. Abnormal pelvic nodes were found in 62 (52.1%) patients, and metastasis was confirmed by histology in 38 (31.9%) patients. Three patients had micro-metastasis in para-aortic nodes, and all of these patients had abnormal pelvic lymph nodes on LUS. CONCLUSION: Abnormal pelvic nodes are commonly found on LUS in patients with advanced-stage cervical cancer, and selective excision biopsy is needed to confirm pelvic node metastasis. Surgical staging of aortic nodes might be considered for patients with abnormal pelvic nodes on LUS.

The technique of laparoscopic pelvic ultrasonography for metastatic lymph node.

Many reports have provided evidence to support the effective use of diagnostic laparoscopy and laparoscopic ultrasonography (LUS) to determine if patients with upper abdominal malignant diseases are operable so that unnecessary laparotomy can be avoided. LUS is less frequently applied to patients with pelvic malignancies and this is probably related to the technical difficulties. We have developed the LUS technique in examining the pelvic nodes for metastasis systematically and have applied it to 241 cervical cancer patients. The procedure is safe and not associated with any major morbidity. The mean duration of pelvic node assessment by LUS is 14 minutes and the procedure can be satisfactorily completed in 98% of patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LUS in detecting pelvic nodal metastasis were 81.2%, 55.6%, 88.4%, 57.7%, and 87.5%, respectively, in patients scheduled for radical hysterectomy. In this report, we describe the LUS technique in detail and demonstrate important landmarks that provide useful orientation during an LUS examination. The technical limitations and pitfalls are also discussed.

Risk factors for squamous intraepithelial lesions in systemic lupus erythematosus: a prospective cohort study.

OBJECTIVE: We undertook a prospective cohort study to ascertain the risk factors for the development of squamous intraepithelial lesions (SIL) in patients with systemic lupus erythematosus (SLE). METHODS: One hundred thirty-seven SLE patients with a normal Papanicolaou (Pap) smear at baseline were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap smear, human papillomavirus (HPV) DNA test, and clinical assessment were performed. RESULTS: Among the 137 patients, there were 12 incident cases (8.8%) of SIL over a median followup duration of 30.7 months (interquartile range 25.5-31.7). Among the 30 patients with HPV infection detectable by DNA testing at baseline, 9 (30%) developed SIL. The independent risk factors for the incident SIL in this group of SLE patients included the use of cyclophosphamide (CYC) ever (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 1.1-29.3; P=0.041) and persistent high-risk HPV infection (OR 26.9, 95% CI 3.2-222.3; P=0.002). The use of baseline HPV testing has a higher sensitivity than abnormal cytology (defined as atypical squamous cells of undetermined significance; 47.7% versus 33.3%) in predicting the development of SIL. CONCLUSION: Independent risk factors associated with the development of SIL in SLE patients included persistent high-risk HPV infection and the use of CYC. Low-risk patients who receive negative test results on both cervical cytology screening and HPV DNA testing may not need to be rescreened within 3 years.

Clinical study of quantitative diagnosis of early cervical cancer based on the classification of acetowhitening kinetics.

A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.

Natural history of cervical papilloma virus infection in systemic lupus erythematosus - a prospective cohort study.

OBJECTIVE: To ascertain the incidence, cumulative prevalence, persistence, and clearance of human papilloma virus (HPV) infection in patients with systemic lupus erythematosus (SLE), and to assess the risk factors for the acquisition and persistence of HPV infection. METHODS: One hundred forty-four patients with SLE were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap test, a test for HPV DNA, and clinical assessment were performed. RESULTS: The cumulative prevalence of HPV infection increased significantly (12.5% at baseline to 25.0% after 3 years; p = 0.006). Regarding type-specific HPV infection, 18.8% patients experienced 68 incident infections. The cumulative prevalence of high-risk HPV infection (11.1% at baseline to 20.8% after 3 years; p = 0.02) and multiple HPV infection also increased significantly (6.9% at baseline to 16.7% after 3 years; p = 0.009). Half (33/68, 48.5%) of the incident infections persisted for >or= 6 months. Overall, 29/32 (90.6%) of the preexisting infection and 10/68 (14.7%) of the incident infections were cleared. Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (p = 0.025) and baseline Systemic Lupus International Collaborating Clinics score >or= 1 (p = 0.038). Independent risk factor associated with persistent HPV infection included preexisting HPV infection (p = 0.04) and multiple HPV infection during first incident infection (p = 0.02). CONCLUSION: High frequency of persistent HPV infection, especially high-risk and multiple HPV infection, may explain why squamous intraepithelial lesions occurred frequently in patients with SLE. Patients with high inflammatory burden are at risk of acquiring HPV infection.

Cryotherapy as the treatment modality of postcoital bleeding: a randomised clinical trial of efficacy and safety.

BACKGROUND: Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management. AIMS: To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding. METHODS: A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment. RESULTS: The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% +/- 35.87 but was only 61.62% +/- 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups. CONCLUSION: Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.