Association between HLA-DRB1 polymorphism, high-risk HPV infection and cervical neoplasia in southern Chinese.

Multiple determinants are involved in the progression of human papillomavirus (HPV)-infected cervical lesion to invasive cancer. Human leukocyte antigen (HLA) polymorphism seems to play a role. This study examined the association between HLA-DRB1 polymorphism, high-risk HPV infection, and the development of cervical neoplasia in southern Chinese. Three hundred and seventy women with cervical neoplasia (43 cervical intraepithelial neoplasia grade II, 154 grade III, and 173 invasive cancers) and 323 controls were recruited for HLA-DRB1 typing by a sequence-based approach. Cervical specimens were collected for HPV detection by a consensus primer-based polymerase chain reaction, and with the type of HPV identified by hybridization with type-specific oligonucleotide probes. A protective effect of HLA-DRB1*12 for cervical neoplasia was observed, and with stronger associations when subgroup analyses were carried out for patients infected with HPV16 and HPV58. The protective effect of HLA-DRB1*13 that had been reported from other populations was not observed. The data obtained in this study showed that HLA-DRB1*03 conferred a higher risk for HPV18-infected, but not for HPV16-, HPV52-, or HPV58-infected cervical lesions. Although, HPV52 was reported as uncommon worldwide, it was found to be the second most prevalent type in the southern Chinese population. However, no additional risk association was observed when subgroup analyses were performed for HPV52-infected patients. The current study shows that, among southern Chinese, the outcome of HPV-infected cervical lesions is associated with HLA-DRB1 polymorphism. These associations often vary with the type of HPV infection.

HLA-B alleles, high-risk HPV infection and risk for cervical neoplasia in southern Chinese women.

A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (p(corrected) = 0.003), and for HPV52-positive CIN III/ICC (p(corrected) = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations.

Biases in human papillomavirus genotype prevalence assessment associated with commonly used consensus primers.

Consensus primers targeting human papillomaviruses (HPVs) have biases in sensitivity toward certain HPV types. We applied 3 primer sets (GP5+/6+, MY09/11, PGMY09/11) in parallel on 120 Chinese cervical cancer specimens. GP5+/6+ exhibited a poor sensitivity for HPV52, for which the prevalence among squamous cell cervical cancer was underestimated from 14.6% to 0%. The fact that HPV52 should rank second in prevalence among squamous cell cervical carcinoma in Hong Kong could be missed if GP5+/6+, a worldwide commonly used primer set, was selected for HPV detection. Biases in HPV type-specific sensitivity may result in misprioritization of vaccine candidates.

Risk association between human leukocyte antigen-A allele and high-risk human papillomavirus infection for cervical neoplasia in Chinese women.

To examine the association between human leukocyte antigen-A (HLA-A) allele polymorphism, human papillomavirus (HPV) infection, and risk for cervical neoplasia in Chinese women, 263 patients (155 with cervical intraepithelial neoplasia [CIN] II/III and 108 with invasive cervical cancer [ICC]) were compared with 572 controls. Overall, regardless of HPV status, a decreased risk for ICC was observed for patients with A*0207/0215N or A*2402, and an increased risk was observed for patients with A*1104. The protective association of A*0207/0215N was reproduced in HPV-16-positive patients with ICC, but not in subgroups infected with other HPV types. The risk association between A*1104 and both HPV-16 and HPV-18 was reproduced in the subgroups with CIN III/ICC. The protective association between A*2402 and HPV-16, HPV-18, HPV-52, and HPV-58 was consistently observed in all subgroups with CIN III/ICC, suggesting a linkage with a general antioncogenic genetic factor. The results of the present study indicate that HLA-A polymorphism is one of the host genetic factors that alter the risk for the development of cervical cancer in Chinese women.