Alexander R. Chang

Determinants of Cervical Human Papillomavirus Infection: Differences between High- and Low-Oncogenic Risk Types

This cross-sectional survey assessed the determinants of human papillomavirus (HPV) infections among 2080 women who participated in cervical cancer screening. HPVs were typed by restriction and sequencing analyses. The prevalence of HPV was 7.3% (4.2% for high-risk, 1.9% for low-risk, and 2.1% for unknown-risk types). High-risk HPV prevalence decreased with age, whereas low- and unknown-risk HPVs had a second peak in older women. Young age was the only common variable associated with the 3 groups of HPV infections. Lifetime number of sex partners was associated with high- and low-risk types but not with unknown-risk HPVs. Previous Pap smear, treatment for cervical lesions, induced abortion, smoking and having smoker(s) in the family were risk factors for high-risk HPVs. Barrier contraception was protective for low-risk HPVs; current vaginal discharge had a negative association with unknown-risk HPVs. The results indicate that different risk profiles exist for infections with different HPV groups.

Age distribution of human papillomavirus infection and cervical neoplasia reflects caveats of cervical screening policies

Although a second age‐related peak of human papillomavirus (HPV) infection is observed in many populations, it does not seem to have any impact on cervical screening policies. We examined the age‐specific prevalence of HPV infection among 2,604 women enrolled for cervical screening and correlated the age at diagnosis of 2,491 cervical intraepithelial neoplasia Grade 2/3 (CIN2/3) lesions and 801 invasive cervical cancers (ICC). Two peaks of HPV infection were detected at 26–30 and 46–50 years, respectively. The first infection peak was followed by a CIN2/3 peak and an ICC peak at 5–15 and 15 years later, respectively. The second infection peak was followed by an ICC peak 20 years later, but strikingly no CIN2/3 peak was detected in between and thus eliminated an opportunity of treating the lesions at preinvasive stages. The most plausible explanation is that women at the expected second CIN2/3 peak (50–65 years) are not having Pap smears under the current opportunistic screening program. Furthermore, women of this age may have physiological retraction of the transformation zone, and CIN lesions may remain undetected if an adequate Pap smear sample is not obtained. To combat this problem, the screening program in Hong Kong needs to focus on women aged 50 years and older and a mop‐up screening up to 75 years is necessary. Bimodal peaks of HPV infection and cervical cancer are seen in many countries and the analysis of population‐specific age distribution of CIN2/3 should be an integral exercise in evaluating the effectiveness of a screening program.

Genetic imbalances in pleomorphic xanthoastrocytoma detected by comparative genomic hybridization and literature review

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumor found in the central nervous system. Histologically, the tumor is characterized by markedly pleomorphic and lipidized cells. Although most of the patients have a favorable prognosis, a small number of cases undergoing recurrence or progression to anaplastic astrocytoma were reported. Very few genetic studies have been performed on PXA because of its rarity and the pathogenesis of this neoplasm is largely unknown. In order to provide an overview of genetic alterations in PXA, we performed comparative genomic hybridization to identify chromosomal imbalances (DNA gains and losses) in three cases of PXA. Genetic imbalance was detected on at least one chromosome for each case. One case, which revealed multiple genetic alterations, showed a poor prognosis. DNA gain on chromosome 7 and loss on 8p were demonstrated in two of three cases, suggesting that the candidate gene(s) located on these regions may play a role in the development of PXA. Further studies are needed to identify the residing candidate genes that are involved in the tumorigenesis of PXA. In addition, the histopathological features and previous genetic studies on PXA are reviewed.

Molecular Evidence for High Frequency of Multiple Paternity in a Freshwater Shrimp Species Caridina ensifera

Background Molecular genetic analyses of parentage provide insights into mating systems. Although there are 22,000 members in Malacostraca, not much has been known about mating systems in Malacostraca. The freshwater shrimp Caridina ensifera blue, is a new species belonging to Malacostraca which was discovered recently in Sulawesi, Indonesia. Due to its small body size and low fecundity, this species is an ideal species to study the occurrence and frequency of multiple paternity and to understand of how the low fecundity species persist and evolve. Methodology/Principal Findings In this study, we developed four polymorphic microsatellites from C. ensifera and applied them to investigate the occurrence and frequency of multiple paternity in 20 C. ensifera broods caught from Lake Matano, Sulawesi. By genotyping the mother and all offspring from each brood we discovered multiple paternity in all 20 broods. In most of the 20 broods, fathers contributed skewed numbers of offspring and there was an apparent inverse correlation between reproductive success of sires and their relatedness to mothers. Conclusions/Significance Our results in combination with recent reports on multiple paternity in crayfish, crab and lobster species suggests that multiple paternity is common in Malacostraca. Skewed contribution of fathers to the numbers of offspring and inverse correlation between reproductive success of sires and their relatedness to mothers suggest that sperm competition occurred and/or pre- and postcopulatory female choice happen, which may be important for avoiding the occurrence of inbreeding and optimize genetic variation in offspring and for persistence and evolution of low fecundity species.

Epidemiologic Risk Profile of Infection With Different Groups of Human Papillomaviruses

This study identified the age‐specific prevalence and epidemiologic risk profile for infection with different groups and species of human papillomaviruses (HPV). Structured interview and HPV testing were conducted for 2,604 Chinese women self‐referred for cervical screening. Independent risk factors for infection were identified by multiple logistic regressions. Overall, a major peak of HPV infection was observed at women aged 26–30 years, and a minor peak at 46–55 years. This pattern was observed for high‐risk, low‐risk, and alpha‐5/7/9 HPVs; but alpha‐3/6 HPVs showed peaks of similar magnitudes in young and older women. Independent risk factors for HPV infection (all types combined) included younger age (OR [95% CI] for >55 vs. ≤30 years = 0.22 [0.09–0.55]; 31‐45 vs. ≤ 30 years = 0.57 [0.33–0.99]), having ≥4 lifetime sexual partners (2.28 [1.06–4.88]), and smoking (2.24 [1.22–4.10]). Young age and smoking were the most consistent independent risk factors observed across different HPV groups. The risk profile for high‐risk HPV was similar to alpha‐5/7/9. Single‐type infection was associated with having more sexual partners, higher education level and oral contraception; whereas multiple‐type infection was associated with smoking. In conclusion, a U‐shaped age‐specific prevalence curve was observed for HPV infection overall, but with a different pattern for different HPV species. Different HPV groups showed variations in their risk profiles. These data are useful for formulating preventative strategy for HPV‐related diseases. Catch‐up vaccination program in Hong Kong should cover a wider age group as the first peak of infection occurred relatively late. J. Med. Virol. 81:1635–1644, 2009.

Can Technology Expedite the Cervical Cancer Screening Process? A Hong Kong Experience Using the AutoPap Primary Screening System With Location-Guided Screening Capability

We studied the usefulness of an automated screening instrument for processing Papanicolaou (Pap) smears to determine whether it could speed human examination by recording the time to screen 1,007 cervical Pap smears with an AutoPap primary screening instrument with location-guided screening (LGS) software and by conventional microscopic examination. We also assessed the accuracy of the methods to determine preparation adequacy, and we compared the diagnosis by each method. The AutoPap with LGS satisfactorily determined the adequacy of Pap smears and identified the marked abnormal cells for human examination. An accurate diagnosis was possible when only the marked cells were examined, and this method reduced the screening time to less than half that required for conventional screening. With low-grade squamous intraepithelial and more severe lesions as a threshold, there were 37 cases in the conventional group and 29 cases in the LGS group. With atypical squamous cells of undetermined significance as the threshold, there were 111 cases in the LGS group and 93 cases in the conventional group. The AutoPap with LGS can significantly speed the examination of Pap smears without lowering the detection rate of clinically important lesions, thus helping alleviate the cytotechnologist shortage.

Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins.

Characterization and cross-species amplification of microsatellites from the endangered Hawksbill turtle (Eretmochelys imbricate)

Twelve novel polymorphic microsatellites were isolated from the endangered Hawksbill turtle (Eretmochelys imbricate). Eight of 12 markers were used to study genetic diversity of two sea turtle species: E. imbricate and green sea turtle (C. mydas). In E. imbricate, the average allele number of the eight microsatellites was 6.25/locus with a range of 3–13. The average expected and observed heterozygosity was 0.66 and 0.63 respectively. In C. mydas, the average allele number of the eight markers was 11.63/locus. The observed heterozyosity (0.68) was lower than the expected heterozyosity (0.79). Most of 12 microsatellites amplified specific and polymorphic PCR products in other six turtle species. Hence, the developed microsatellites would facilitate studies on genetic diversity and population structure of E. imbricate and other marine turtle species.

The usefulness of cytodiagnosis and DNA cytometry on nasopharyngeal brush smears for the diagnosis of nasopharyngeal carcinoma.

To assess the usefulness of combining cytodiagnosis and DNA cytometry on nasopharyngeal brush samples for the detection of nasopharyngeal carcinoma (NPC).

Cervical cytology screening in Vietnamese asylum seekers in a Hong Kong detention center: Population demographics and historical perspectives

OBJECTIVE To provide a brief review of the history and demographics of the Vietnamese asylum-seeking population in Hong Kong and their possible effects on the initiation of a cervical cytology screening program at a Hong Kong detention center. STUDY DESIGN Analysis of case histories, questionnaires and interviews with women in a detention center identified demographic features related to Pap smear history, knowledge of the Pap test, age at first intercourse and cigarette smoking status among women aged 17 years and over. Analysis of Pap smear uptake following initiation of a screening program was undertaken. RESULTS Of the 1,171 women in the detention center who were eligible for a Pap smear, 536 (45.8%) actually obtained one, although enrollment, which was strong at the initial offering, slowed considerably as the program progressed. None of the women had had a Pap smear prior to leaving Vietnam. Knowledge of the utility and risk status criteria for Pap testing was very limited. The majority (77.9%) of the subjects started sexual activity after age 20 years, and three (0.6%) smoked. There were four (0.2%) abnormal smears identified among those tested. CONCLUSION Convincing evidence was obtained that the Pap test was not widely used in Vietnam among the asylum-seeking population, and its role in preventing cervical cancer was not well known to the women studied. The initial strong uptake of the Pap smear was not maintained. That may be attributable to psychosocial factors associated with detention under harsh conditions and trauma associated with fleeing Vietnam.