Teresa Apresa-García

Association between high-risk human papillomavirus DNA load and precursor lesions of cervical cancer in Mexican women

OBJECTIVE Our objective was to determine the association between viral load of high risk human papilloma virus (HPV) using the Hybrid Capture II (HC II) system and cervical intraepithelial neoplasia (CIN) lesion stage. METHODS A total of 182 consecutive women with confirmed diagnoses of CIN 1-3 and 182 healthy women with negative Pap were included. All subjects underwent structured interviews focused on socioeconomic and reproductive factors. HC II testing was used to detect human papilloma virus (HPV) DNA. Viral load was measured by light measurements expressed as relative lights unit (RLU) ratio (specimens/control). Log(10)RLU ratios were categorized for analysis into four groups: negative (</=0); low viral load (0.01-1.0), middle viral load (1.01-2.0), and high viral load (2.0-3.6). Frequencies and association measurement odds ratio (OR) adjusted by unconditional multinomial regression (UMR) were used in analysis. RESULTS A total of 75 of 80 (93.7%) patients with CIN 2-3, 82 of 101 (79.4%) with CIN 1, and 36 of 182 (19.8%) controls were positive for HPV DNA. The higher the viral load of HPV DNA infection observed, the higher the probability of being associated with stage of CIN (P <0.001). Association between low viral load HPV and CIN 1 was 16.8 (7.2-39) compared with the highest association observed with high viral load and CIN 2-3 (OR(a) = 365.8, 94.7-1412). Both control and cases in the oldest women presented the highest viral load. CONCLUSIONS We found high frequencies of HPV DNA in CIN 1 and in CIN 2-3 patients. A clear association between viral load of HPV DNA was determined by HC II assay and CIN stage.

Human papillomavirus genotypes among females in Mexico: a study from the Mexican institute for social security.

BACKGROUND The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Human leukocyte antigens I and II haplotypes associated with human papillomavirus 16-positive invasive cervical cancer in Mexican women.

Infection with human papillomavirus (HPV), mainly HPV type 16, is the major etiologic factor associated with cervical cancer (CC), but HPV infection alone is not sufficient for progression of precursor lesions. Host genetic susceptibility may lead to abnormal immune response resulting from virus persistence. Several studies have suggested a possible association with specific human leukocyte antigen (HLA) class I and II alleles and CC, but results are not consistent. The association of genetic HLA class I (A and B) and HLA class II (DR*B1 and DQ*B1) haplotypes with HPV16-positive CC (n = 104) and base population controls (n = 104) was evaluated in this Mexican population study. Sequence-specific primer HLA genes were determined by polymerase chain reaction (PCR)-based methods in peripheral blood cell counts (PCR sequence-specific oligonucleotides). The cervical swabs of 208 women were tested for HPV16 by Hybrid Capture II. Allele and haplotype HLA frequencies, Hardy-Weinberg tests, and a haplotype homogeneity test were estimated using the Arlequin software v. 3.01. Odds ratio (OR) was calculated to compare cases and control women. Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women. The HLA-A2-B44-DR4-DQ*0302, HLA-A24-B35-DR16-DQ*0301, and HLA-A2-B40-DR4-DQ*0302 haplotypes showed a positive association with CC (OR, >1), whereas HLA-A2-B39-DR4-DQ*0302, HLA-A24-B35-DR4-DQ*0302, and HLA-A68-B40-DR4-DQ*0302 showed a negative association (OR, <1). These results support the hypothesis that some HLA class I and II haplotypes could be involved with susceptibility for developing CC. Abbreviations: Cervical Cancer-CC, confidence interval-CI, human leukocyte antigens-HLA, human papillomavirus-HPV, odds ratio-OR, polymerase chain reaction-PCR, relative risk-RR, relative light units-RLU, ribonucleic acid-RNA, sequence-sensitive oligonucleotide-SSO

A non-invasive tool for detecting cervical cancer odor by trained scent dogs

BackgroundCervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population’s quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC.MethodsUsing clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle’s ability to discriminate CC from control samples.ResultsThe beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle’s success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients.ConclusionPresent data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Volatolome of the Female Genitourinary Area: Toward the Metabolome of Cervical Cancer

BACKGROUND AND AIMS Different Volatile Organic Compounds (VOCs) obtained from several human fluids (volatolome) has been reported as potential biomarkers for a great variety of diseases including cancer. At present, volatolomic profile data of the female genital area is scarce. METHODS To identify the VOCs related to the female genitourinary area of healthy and Cervical Cancer (CC)-affected women used a pad, as a non-invasive tool for sample gathering was necessary. Used pads were analyzed by Gas Chromatography-Mass Spectrometry. The data were subjected to Principal Component Analysis looking for a possible spectrum of VOCs that could help identify CC-affected patients. The diagnostic role of the VOCs was validated through Receiver Operating Characteristic (ROC) analysis. The area below the curve and the diagnostic sensitivity and specificity values were also evaluated. RESULTS The data showed great differences between female cancer and healthy patients groups; most of these VOCs belonging to the alkanes chemical classes. A group of VOCs were identified as common among CC patients, while others VOCs for healthy females. The ROC curve showed an optimal reach to diagnosis (89%), returning a 93% rate for sensitivity and specificity, indicating the VOCs identified in the samples could differentiate cancer patients from healthy females. CONCLUSIONS In summary, we have detected and identified specific VOCs from healthy women that are not present in CC-affected females and VOCs specific of CC-affected women. We are strengthening our findings to aid in the detection of VOCs that are potential biomarkers for cervical tumors.