High-risk Human Papillomavirus Infection In Women Research Articles

Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk

Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. The aim of this study was to investigate whether some GST polymorphisms could influence the risk to develop CC, either by themselves or in combination with smoking habit, in a cohort of high-risk HPV (HR-HPV) infected Italian women. The study population comprises 192 Italian women including 81 HR-HPV infected women bearing cervical lesions and 111 healthy controls. The cases include: 26 low-grade squamous intraepithelial lesions (LSILs), 30 high-grade-SIL, and 25 CCs, while controls were all negative for HPV. DNA was extracted from peripheral blood samples or cytobrush and individuals were genotyped for GSTM1, GSTT1, and GSTP1 polymorphisms using PCR and PCR/RFLP techniques. On studying the association of GSTs gene polymorphisms with cervical cancer lesions, the combination of GSTM1 null, GSTT1 null and GSTP1 AA genotypes, independently on smoking habit, seems to be related to a 5.7-fold increased risk of developing CLs with a considerable statistical significance (P = 0.0091). We suggest that the investigation of multiple gene polymorphisms, versus single genes, could contribute to a better understanding of the effect of susceptibility genes on cancer risk.

MBL2 gene polymorphisms are correlated with high-risk human papillomavirus infection but not with human papillomavirus–related cervical cancer

We investigated whether there is a correlation between MBL2 polymorphisms and the host susceptibility to human papillomavirus (HPV) infection and cancer development. Toward this end, we analyzed MBL2 exon 1 polymorphisms in 172 women infected by strains of HPV that are associated with high-risk of cervical cancer development (or “high-risk” HPV infection), 105 of whom had HPV-related squamous cell carcinoma of the cervix (SCC), as well as 105 women not infected by HPV. We demonstrated an association of MBL2 polymorphisms with high-risk HPV infection in women without SCC who showed increased presence of the mutant MBL2 0 allele and 0/0 genotype as compared with women with SCC and healthy controls. No correlation with MBL2 polymorphisms was found in women who developed cancer. Therefore we propose that MBL2 polymorphisms responsible for defective production of mannose binding lectin (MBL) protein play a role in the increased susceptibility to high-risk HPV infection but not to cervical cancer onset and development.

Chromosome aberrations in peripheral blood lymphocytes of high‐risk HPV‐infected women with HGSIL

Genomic instability is one of the main characteristics of malignant tumors, including HPV-induced cervical cancer. The aim of this study was to explore the use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a biomarker for genomic instability in high-risk HPV-infected women with high-grade squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for this study, following cytology/colposcopy evaluation and HPV DNA detection. The study groups consisted of 30 HPV(+) women with histologically confirmed cervical intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ (CIS). Two control groups, including 30 women HPV(-) and 30 women HPV(+), were recruited among women who were reported as cytology negative. Lymphocyte cell cultures were established for 52 hr, and 100 complete metaphase cells were evaluated per subject for CA analysis. The results show that women with CIS had significantly higher frequencies of both aneuploidy (0.67 +/- 0.20 vs. 0.14 +/- 0.08, P = 0.020) and tetraploidy (0.88 +/- 0.23 vs. 0.17 +/- 0.08, P = 0.013) in comparison with HPV(-) controls. These findings suggest the usefulness of peripheral blood lymphocytes to detect genomic instability associated with HPV-induced HGSIL.

Association between MBL2 gene functional polymorphisms and high-risk human papillomavirus infection in Brazilian women

We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functional polymorphisms in a group of 180 high-risk HPV-infected women and 180 healthy control subjects. The most frequent high-risk HPV genotypes were 16 (47.2%), 31 (11.7%), 33 (5%), and 18 (2.2%), respectively. Of the 180 HPV-infected women, 99 presented with uterine cervical cancer and 81 did not. No differences in MBL2 genotype or in allelic or haplotype frequencies were found between HPV patients who developed cervical uterine cancer and those who did not. When considering combined genotypes grouped according to MBL production (designated as high, low, and deficient producers), we detected a significant difference between healthy controls and high-risk HPV-positive patients, the latter group showing increased frequencies of deficient-producer genotypes (14.4% vs 9.4% in the healthy control group, corrected p = 0.04). In conclusion, a correlation between MBL2 polymorphisms and high-risk HPV infection was found in this study.

The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix

To investigate intralesional cytokine levels in precancerous lesions of the uterine cervix and their relationship with human papillomavirus (HPV) type 16, HPV type 16 E6/E7, and high-risk HPV viral load. We performed a prospective study of 67 patients between May 2005 and December 2005. Hybrid Capture II testing was used to identify patients as high-risk HPV DNA-positive or -negative. HPV DNA Chip test was performed for HPV genotyping in all cases found to be HPV DNA-positive. Real-time PCR was used to quantify HPV-16 E6, E7, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) transcripts. Among high-risk HPV-infected women, intralesional TNF-alpha, IL-6, IL-10, and IFN-gamma levels had no significant differences according to histologic grade. In multivariate logistic regression analysis, TNF-alpha, IL-6, IL-10, and IFN-gamma were not associated with HPV-16. Increased IFN-gamma was significantly associated with HPV-16 E6- and E7-positive (OR 28.197, 95% CI: 2.658-299.110; OR 19.617, 95% CI: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. In multiple regression analysis, elevated IFN-gamma was significantly associated with increased HPV viral load (P=0.039), whereas TNF-alpha, IL-6, and IL-10 were not significantly associated with HPV viral load. Among HPV-infected women, IFN-gamma is significantly associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional IFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.

Prevalencia de la infección por el virus del papiloma humano en mujeres con citologías anormales del cérvix uterino y factores de riesgo asociados a la infección

Objectives To determine the prevalence of human papillomavirus (HPV) infection in women with an abnormal pap smear of the uterine cervix and to determine the risk factors associated with HPV infection. Subjects and methods Eighty-one women with a cytological result of atypical cells of unknown origin (ASCUS), low-grade squamous intraepithelial lesions (LG-SIL) or high-grade squamous intraepithelial lesions (HG-SIL) were referred for epidemiological questionnaire, HPV detection performed using the Hybrid Capture II ® test, histological study, and analysis of other sexuallytransmitted diseases. Results Cytologic study identified 16 women with ASCUS, 44 with LG-SIL and 21 with HG-SIL. The global prevalence of HPV infection was 67.9% (55 patients) and high-risk HPV (HR-HPV) infection was detected in 50 patients (61.8%). The percentages of HR-HPV infection in women with ASCUS, L-SIL and H-SIL were 31.2%, 63.6% and 80.9%, respectively. The number of sexual partners over a woman’s lifetime was significantly associated with HPV infection (χ 2 for trend: 4.187; p = 0.0407). Conclusions Women with ASCUS detected by cytology are those who could most benefit from HR-HPV detection techniques, because of the lower prevalence of the infection. The main risk factor associated with HPV infection was the number of sexual partners over a woman’s lifetime.