Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma.

OBJECTIVES: Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial. METHODS: The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas. RESULTS: In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months; P = 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months; P = 0.002). CONCLUSIONS: Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

Ethnic patterns of cytologic abnormalities in cervical smears in suriname, a high-risk area for cervical cancer.

OBJECTIVE: To determine the prevalence of cytologic abnormalities in cervical smears from women attending the first organized screening program in Suriname and to compare the prevalences in 4 Surinamese ethnicities with different cervical carcinoma incidences. STUDY DESIGN: Cervical scrapes were taken from women with 4 different ethnicities: Maroons, Amerindians, Javanese and Hindustani. Papanicolaou staining and cytologic screening were performed on 807 cervical smears. RESULTS Cervical cytologic abnormalities were seen in 13.4%, of which 8.1% (62 of 764) had atypical changes, 2.6% (20 of 764) had mild and 2.6% (20 of 764) had moderate and severe dysplasia/carcinoma in situ (CIS). The cytologic abnormalities varied between the ethnicities: 42.1% (83 of 197) in the Maroons and 2.3% (4 of 176), 5.0% (9 of 183) and 3.0% (6 of 208) in the Javanese, Amerindians, and Hindustani, respectively. CONCLUSION: The high prevalence of moderate and severe dysplasia/CIS in all ethnicities correlates with the high cervical carcinoma incidence in Suriname. A significantly higher prevalence of mild abnormalities in the Maroons was observed; it did not reflect the relatively low cervical cancer incidence in this ethnicity. However, this can be explained by the possibility that these women have a different sexual lifestyle, leading to a higher prevalence of

Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries.

In cervical cancer, human papillomavirus type 18 (HPV 18) and HPV 16 are predominantly related to adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs), respectively. Here, we studied whether the geographically distributed HPV intratypic variants are also associated with histologically different tumors. A total of 44 HPV 18-positive and 91 HPV 16-positive cervical carcinomas from Indonesian, Surinamese and Dutch patients were histologically classified using hematoxilin and eosin, periodic acid Schiff plus and Alcian Blue staining. Samples were sequenced and intratypic variants were classified into the known phylogenetic branches. The Asian Amerindian HPV 18 variant was observed in 56% of ADCs compared to 15% of SCCs (p < 0.006). The African HPV 18 variant was exclusively found in SCCs. By sequencing the HPV 18 E6 and E7 open reading frames, we found predicted amino acid changes only in 8 samples. Two amino acid changes were consistent throughout the African branch. In HPV 16-positive tumors, we did not find a specific linkage between intratypic variants and histopathology. We conclude that HPV 18 intratypic variants are differentially associated with adenocarcinoma and squamous cell carcinoma of the cervix. The findings described here stress the biologic significance of intratypic HPV variants and might help explaining differences in the pathogenesis of cervical ADCs and SCCs.

Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands.

OBJECTIVE: Human papillomavirus type 16 (HPV 16) has several intratypic variants, and some are associated with enhanced oncogenic potential. For risk determination as well as for future vaccine development, knowledge about variants is important. Regarding the geographical distribution of HPV variants and the lack of data from Indonesia and Suriname, we studied the prevalence of HPV 16 variants in cervical cancer in these high incidence countries. Data were compared with The Netherlands, a low-risk country. METHODS: DNA samples from 74 formalin-fixed paraffin-embedded HPV 16-positive cervical carcinomas from Indonesia (Java, N = 22), Suriname (N = 25), and The Netherlands (N = 27) were amplified using primers specific for the E6, E7, and part of the L1 regions. Products were sequenced and analyzed. RESULTS: A specific Javanese variant, with mutations 666A in E7 and 6826T in L1, was found in 73% of the Indonesian samples, 56% having an additional mutation in the E6 open reading frame (ORF; 276G), giving the predicted amino acid change N58S. This Javanese variant was also found in three Surinamese samples, which reflects what could be expected from migration of Javanese people to Surinam. Other non-European variants were identified in Indonesian, Surinamese, and Dutch samples in 14%, 28%, and 19%, respectively. CONCLUSION: The majority of the HPV 16-positive cervical cancers in Indonesia are caused by a specific intratypic variant that was rarely found before in other countries.

Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia.

OBJECTIVES: Cervical cancer is the second most frequently occurring type of cancer in women worldwide. A persistent infection with high-risk human papillomavirus (HPV) is a necessary causal factor in cervical carcinogenesis. The distribution of HPV types in populations has been studied worldwide. In Indonesia, however, few data are available describing the prevalence of HPV. Cervical carcinoma is the most common female cancer in Indonesia and causes high morbidity and mortality figures. With HPV vaccination studies in progress, it is important to map the HPV status of a population that would benefit greatly from future prevention programs. METHODS: We tested 74 cervical cancer specimens from consecutive, newly diagnosed cervical cancer patients in the outpatient clinic of the Dr. Cipto Mangunkusumo Hospital, Jakarta. After additional staining, the formalin-fixed, paraffin-embedded tissue samples were histologically classified. HPV presence and genotype distribution were determined by SPF10 polymerase chain reaction and line probe assay. RESULTS: HPV DNA of 12 different HPV types was detected in 96% of the specimens. The three most common types were 16 (44%), 18 (39%) and 52 (14%). In 14% of the specimens, multiple HPV types were present. The multiple HPV types were significantly more prevalent among adenosquamous carcinomas in comparison with squamous cell carcinoma or adenocarcinoma (P = 0.014). CONCLUSIONS: Distribution of HPV types in Indonesia with a more prominent role for HPV 18 is slightly different from that in other parts of the world. The high amount of multiple HPV infections found in adenosquamous carcinomas may prompt further research on the pathogenesis of this type of cervical tumours.