Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty.

MAGEL2 is one of five protein-coding, maternally imprinted, paternally expressed genes in the Prader-Willi syndrome (PWS)-critical domain on chromosome 15q11-q13. Truncating pathogenic variants of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild-type (WT) allele and a paternally inherited Magel2-lacZ knock-in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader-Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism-like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three-chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in-depth investigation of behavioral profiles caused by Magel2 loss-of-function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general.

Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient.

Organisms of the genus Acanthamoeba are environmentally ubiquitous and colonizers of the oral mucosa in humans. While largely asymptomatic in healthy persons, Acanthamoeba infection can cause disseminated disease with poor prognosis in immunosuppressed populations. Here we report a unique case of cutaneous amoebiasis associated with continuous positive airway pressure use in an immunosuppressed patient.

Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator.

Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.

Impact of lymphadenectomy in uterine endometrioid carcinoma.

AIMS: To investigate the role of lymphadenectomy in uterine endometrioid carcinoma based on the 2009 FIGO staging system. METHODS: Using an institution-maintained cancer registry database, all patients who were treated surgically for endometrial cancer from 1991 to 2008 in two medical centers were analyzed. Kaplan-Meier and Cox proportional hazards methods were used to determine the role of lymphadenectomy. RESULTS: From 961 women with uterine endometrioid carcinoma, 680 underwent lymphadenectomy and 281 did not. Young age, early-stage disease, low-grade tumor, and lymphadenectomy were favorable independent prognostic factors. The five-year disease-specific survival (DSS) of stages IA, IB, II, and III, and the two-year DSS of stage IV patients who underwent lymphadenectomy were 97.8%, 88.3%, 91.5%, 70.5%, and 32.1%, respectively, compared to 98.7%, 70.0%, 73.3%, 42.9%, and 16.6% in those without lymphadenectomy (p > 0.05 for stage IA; p < 0.01 for stages IB-IV, log-rank test). In high-risk patients (i.e., poorly-differentiated, outer-half myometrial invasion, and stages II-IV), more extensive lymph node resection was associated with an improved five-year DSS, from 71.3% (1-10 nodes removed) and 85.3% (11-20 nodes removed) to 86.8% (>20 nodes removed) (p = 0.02, log-rank test). For stage IIIC-IV patients with nodal metastasis, the extent of node resection also significantly improved the five-year DSS, from 34.4% (1-10 nodes removed) and 62.4% (11-20 nodes removed) to 79.6% (>20 nodes removed) (p = 0.04, log-rank test). CONCLUSIONS: Lymphadenectomy improves the survival of patients with uterine endometrioid carcinoma stage IB to stage IV. The extent of lymphadenectomy also improves the survival of high-risk patients and those with nodal disease.

Cardiac iron measurement and iron chelation therapy in patients with ß thalassaemia major: experience from Taiwan.

BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.

Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures.

AIM: To report several types of response of immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscess to revascularization procedures. METHODOLOGY: Twenty immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscesses from 20 patients were included. The teeth were isolated with rubber dam, and pulp chambers was accessed through the crowns. The canals were gently irrigated with 5.25% sodium hypochlorite with minimal mechanical debridement. Calcium hydroxide was used as an inter-appointment intracanal medicament and placed into the coronal half of the canal space. After resolution of clinical signs and symptoms, bleeding was induced into the canal space from the periapical tissues using K-files. The coronal canal space was sealed with a mixture of mineral trioxide aggregate (MTA) and saline solution. The access cavity was filled with composite resin. These immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscesses were followed up from 6 to 26 months. RESULTS: Five types of responses of these immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures were observed: type 1, increased thickening of the canal walls and continued root maturation; type 2, no significant continuation of root development with the root apex becoming blunt and closed; type 3, continued root development with the apical foramen remaining open; type 4, severe calcification (obliteration) of the canal space; type 5, a hard tissue barrier formed in the canal between the coronal MTA plug and the root apex. CONCLUSIONS: Based on this case series, the outcome of continued root development was not as predictable as increased thickening of the canal walls in human immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess after revascularization procedures. Continued root development of revascularized immature permanent necrotic teeth depends on whether the Hertwig's epithelial root sheath survives in case of apical periodontitis/abscess. Severe pulp canal calcification (obliteration) by hard tissue formation might be a complication of internal replacement resorption or union between the intracanal hard tissue and the apical bone (ankylosis) in revascularized immature permanent necrotic teeth.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population.

OBJECTIVE: To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). DESIGN: Prospective study of a screened population. POPULATION: Case series from nationwide screening population. METHODS: The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. MAIN OUTCOME MEASURES: Diagnosis of cervical, uterine, or ovarian cancers. RESULTS: Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). CONCLUSIONS: Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear).

Brain metastasis as a late manifestation of ovarian carcinoma.

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Cost-effectiveness analysis of human papillomavirus DNA testing and Pap smear for cervical cancer screening in a publicly financed health-care system.

OBJECTIVE: to evaluate the long-term cost-effectiveness of different strategies for human papillomavirus (HPV) DNA testing combined with Pap smear for cervical cancer screening in Taiwan. METHODS: this study adopts a perspective of Department of Health in cost-effectiveness analysis to compare a no-screening strategy with nine different screening strategies. These strategies comprise three screening tools (Pap smear alone, HPV DNA testing followed by Pap smear triage, and HPV DNA testing combined with Pap smear), and three screening intervals (annually, every 3 years, and every 5 years). Outcomes are life expectancy, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analyses (PSAs) were conducted to assess parameter uncertainty. RESULTS: when three times gross domestic product per capita is used as the decision threshold, all nine screening strategies were cost-effective compared with the no-screening strategy. Compared with the current screening strategy (an annual Pap smear), HPV DNA testing followed by Pap smear triage every 5 years and every 3 years were cost-effective. Results of PSA also indicated that a HPV DNA testing followed by Pap smear triage every 5 or every 3 years achieved the highest expected net benefits. CONCLUSIONS: possible economic advantages are associated with extending the cervical cancer screening interval from one Pap smear annually to HPV DNA testing followed by Pap smear triage every 5 years with an ICER $1 247 000 per QALY gained, especially in a country with a publicly financed health-care system.

Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences.

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006. The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23-3.37) P=0.006) and OS (3.72 (1.64-8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76-125.60), P=0.013) or suboptimal (4.47 (1.83-10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

Synchronous primary cancers of the endometrium and ovary.

Simultaneous detection of malignancy in the endometrium and ovary represents an uncommon event. The objective of the study was to clarify the possible factors that influenced on the survival. From 1977 to 2005, totally 27 patients fulfilled the criteria and were included in the study. The medical records and the pathologic reports were reviewed. The histologic determination was followed by the World Health Organization Committee classification, and cancer stage was based on the staging system of the FIGO. The Kaplan-Meier survival analyses were generated and compared by the log-rank test. The incidence of synchronous primary endometrial and ovarian cancers was 3.3% in patients with endometrial cancer and 2.7% in patients with ovarian cancer. The mean survival in the group of similar histology (n= 15) was 63 months, and 48 months in the group of dissimilar histology (n= 12) (P= 0.63). The mean survival in the group of early stage (n= 21) was 68 months and 15 months in the group of advanced stage (n= 6) with statistic significance (P= 0.0003). However, the impact of adjuvant therapy on survival did not reach statistic significance (P= 0.15 for chemotherapy; P= 0.69 for radiotherapy). We conclude that the majority of the patients belonged to concordant endometrioid histology in endometrium and ovary, and it tends to be early stage and low grade with favorable prognosis. The stage had more significant influence on the survival than the histology. Adjuvant therapy should be given especially in patients with advanced stage although the optimal management remained to be determined.

Intracerebral hemorrhage as initial presentation of gestational choriocarcinoma: a case report and literature review.

Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. One rare case of metastatic cerebral choriocarcinoma with initial presentation of intracerebral hemorrhage is reported. A 40-year-old woman initially presented sudden onset of headache. Intracerebral hemorrhage resulting from ruptured pseudoaneurysm was suspected. Emergent surgery with excision of the pseudoaneurysms was performed. Metastatic choriocarcinoma was accidentally found with positive immunohistochemical staining of cytokeratin and beta subunit of human chorionic gonadotropin (beta-HCG). Choriocarcinoma with brain metastases was diagnosed. She then received chemotherapy with regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (EMACO). Elevated serum beta-HCG (30.3 mIU/mL) and new pulmonary lesions were noted by computed tomography 4 months after completion of EMACO. Salvage chemotherapy with etoposide, methotrexate, actinomycin-D, etoposide, and cisplatin (EMAEP) regimen was given. Seven months later after completion of EMAEP, two new pulmonary lesions were detected by positron emission tomography (PET) scan. So she received video-assisted thoracoscopic surgery with tumor excision. Pathologic report confirmed the diagnosis of lung metastases. The patient recovered well. She is free of disease for 12 months. The diagnosis of metastatic cerebral choriocarcinoma was only made by histopathology after craniotomy. Metastatic choriocarcinoma should be always in the differential diagnosis for women at childbearing age presenting with unexplained stroke-like symptoms. In addition, PET scan may be valuable in detecting occult metastatic lesions of choriocarcinoma.

Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix.

To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9-29.4, P<0.01), as evaluated by real-time PCR and a 44% risk (OR=6.1, 95% CI=1.6-22.7, P<0.01), as evaluated by HC2. The two viral load measures correlated well (Person's coefficient, r=0.687, P<0.001). Such evaluations of viral load changes (increased or not increased) through repeat HPV DNA testing could predict progression of disease in LSIL cases of HPV types 16, 18, 52, and 58, which correlates to clinical implications.

The distribution and differential risks of human papillomavirus genotypes in cervical preinvasive lesions: A Taiwan Cooperative Oncologic Group Study.

To clarify the distribution and relative risk of different human papillomavirus (HPV) genotypes in cervical preinvasive lesions, 1246 women with abnormal Papanicolaou smear including atypical squamous cell of unknown significance (ASCUS), atypical glandular cell of unknown significance (AGUS), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) were enrolled in a multicenter, cross-sectional study. Colposcopy and HPV tests with hybrid capture 2 and polymerase chain reaction-reverse line blot were performed. The prevalences of HPV in ASCUS/AGUS-negative histology, ASCUS/AGUS, LSIL, HSIL, and invasive cancer were 33.8%, 38.3%, 74.9%, 84.3% and 100%, respectively, with an overall positive rate of 68.8%. The most common HPV types were HPV 16 (18.5%), 52 (16.5%), 58 (13.2%), 33, 51, 53, 18, 39, 59, 66, MM8, and 31. In comparing the relative risk of HPV infection in different disease status, LSIL and HSIL/carcinoma had a 4.64 (95% CI: 2.98-7.24) and 10.53 (95% CI: 6.69-16.58) folds of risk of high-risk HPV infection than the negative group. The same was true in mixed HPV infection, but not in low-risk type infection. Looking into each high-risk HPV type, the relative infection risks for LSIL and HSIL/carcinoma, in comparison with the negative group, were 1.67 (0.63-4.43) and 8.67 (3.46-21.70), 2017 (1.01-4.68) and 3.04 (1.42-6.47), and 1.40 (0.52-3.77) and 5.22 (2.07-13.19) for HPV type 16, 52 and 58, respectively. The study confirmed the high prevalence and risky nature of HPV 52 and 58 in Taiwanese population and conveyed the need to include these HPV types in vaccine development.