Plasma Protein Profiles Differ Between Women Diagnosed with Cervical Intraepithelial Neoplasia (CIN) 1 and 3

Early detection of precancerous cells in the cervix and their clinical management is the main purpose of cervical cancer prevention and treatment programs. Cytological findings or testing for high risk (HR)-human papillomavirus (HPV) are inadequately sensitive for use in triage of women at high risk for cervical cancer. The current study is an exploratory study to identify candidate surface-enhanced laser desorption/ionization (SELDI) time of flight (TOF) mass spectrometry (MS) protein profiles in plasma that may distinguish cervical intraepithelial neoplasia (CIN 3) from CIN 1 among women infected with HR-HPV. We evaluated the SELDI-TOF-MS plasma protein profiles of HR-HPV positive 32 women with CIN 3 (cases) and 28 women with CIN1 (controls). Case-control status was kept blinded and triplicates of each sample and quality control plasma samples were randomized and after robotic sample preparations were run on WCX2 chips. After alignment of mass/charge (m-z values), an iterative method was used to develop a classifier on a training data set that had 28 cases and 22 controls. The classifier developed was used to classify the subjects in a test data set that has six cases and six controls. The classifier separated the cases from controls in the test set with 100% sensitivity and 100% specificity suggesting the possibility of using plasma SELDI protein profiles to identify women who are likely to have CIN 3 lesions

Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs)

BACKGROUND: Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs), the causative agent for developing invasive cervical cancer (CC) and its precursor lesions. OBJECTIVE: The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women. METHODS: The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2) assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative) as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity, type of fuel used for cooking and smoking status. RESULTS: Women with higher concentrations of serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being positive for HR-HPVs compared to those with serum folate ≤6 ng/mL and serum vitamin B12 ≤ 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08-0.89; P = 0.03). CONCLUSIONS: These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India

Aflatoxin levels, plasma vitamins A and E concentrations, and their association with HIV and hepatitis B virus infections in Ghanaians: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Micronutrient deficiencies occur commonly in people infected with the human immunodeficiency virus. Since aflatoxin exposure also results in reduced levels of several micronutrients, HIV and aflatoxin may work synergistically to increase micronutrient deficiencies. However, there has been no report on the association between aflatoxin exposure and micronutrient deficiencies in HIV-infected people. We measured aflatoxin B₁albumin (AF-ALB) adduct levels and vitamins A and E concentrations in the plasma of HIV-positive and HIV-negative Ghanaians and examined the association of vitamins A and E with HIV status, aflatoxin levels and hepatitis B virus (HBV) infection.</p> <p>Methods</p> <p>A cross-sectional study was conducted in which participants completed a demographic survey and gave a 20 mL blood sample for analysis of AF-ALB levels, vitamins A and E concentrations, CD4 counts, HIV viral load and HBV infection.</p> <p>Results</p> <p>HIV-infected participants had significantly higher AF-ALB levels (median for HIV-positive and HIV-negative participants was 0.93 and 0.80 pmol/mg albumin, respectively; p <0.01) and significantly lower levels of vitamin A (-16.94 μg/dL; p <0.0001) and vitamin E (-0.22 mg/dL; p <0.001). For the total study group, higher AF-ALB was associated with significantly lower vitamin A (-4.83 μg/dL for every 0.1 pmol/mg increase in AF-ALB). HBV-infected people had significantly lower vitamin A (-5.66 μg/dL; p = 0.01). Vitamins A and E levels were inversely associated with HIV viral load (p = 0.02 for each), and low vitamin E was associated with lower CD4 counts (p = 0.004).</p> <p>Conclusions</p> <p>Our finding of the significant decrease in vitamin A associated with AF-ALB suggests that aflatoxin exposure significantly compromises the micronutrient status of people who are already facing overwhelming health problems, including HIV infection.</p

Mild obesity, physical activity, calorie intake, and the risks of cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: We enrolled 1125 women (age, 18-65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. RESULTS: Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5-23 kg/m(2)), the multivariate ORs (95% CIs) for those overweight (23-25 kg/m(2)) and mild obesity (≥25 kg/m(2)) were 1.25 (0.79-2.00) and 1.70 (1.10-2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61-1.48) and 0.61 (0.38-0.98) for women with medium physical activity (38.5-71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend  = 0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40-1.01) and 0.58 (0.36-0.93) for the medium and high physical activity groups, respectively (p for linear trend  = 0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. CONCLUSION: Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer

The accuracy of HPV genotyping in isolation and in combination with CD4 and HIV viral load for the identification of HIV‐infected women at risk for developing cervical cancer

Abstract Background Human papillomavirus (HPV) genotype testing has limited utility to identify human immunodeficiency virus‐infected (HIV+) women's risk for developing cervical cancer (CC) due to high positivity rate of high‐risk (HR) HPVs. We investigated the accuracy of HPV testing in isolation/in combination with CD4 and HIV viral load (VL) to identify HIV+ women at risk for developing CC. Methods Study consisted of 344 HIV+ women on combination antiretroviral therapy (cART), tested for cervical cytology/HPV using the Cobas test and had data on absolute CD4 count and VL measurements. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of HPV testing, pre‐, post‐cART, and current CD4 and VL in isolation and in combinations to identify those with or free of higher than atypical squamous cells of unknown significance (ASCUS+) or low‐grade intraepithelial lesions (LSIL+). Results HPV test in combination with pre‐/post‐cART or current CD4 counts and VL had higher PPVs compared to HPV test alone for identifying ASCUS+ or LSIL+. PPV of HPV‐CD4 combinations yielded higher PPVs compared to HPV‐VL combinations. The NPVs with pre‐, post‐cART, or current CD4 count and VL in isolation or in combinations were comparable to that of HPV test alone. Conclusions Our results provide a more accurate tool for managing HIV+ women by combining Cobas HPV with CD4 and VL, especially those who had an undesirable pre‐cART CD4 and VL status. Our results also indicate the usefulness of CD4 and VL measurements to identify those at lower risk in the absence of HPV testing

Sociodemographic, reproductive, anthropometric, and lifestyle characteristics of study subjects.

<p>CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; BMI, body mass index; MET, metabolic equivalent; SD, standard deviation.</p>1<p>Analysis of variance for continuous variables and χ² test for categorical variables.</p>2<p>Values in rows with different superscripts are significantly different from each other.</p

Association of total calorie intake and physical activity with the risk of CIN1, CIN2/3, and cervical cancer.

<p>ORs, odds ratios; 95% CIs, 95% confidence intervals; CIN, cervical intraepithelial neoplasia; MET, metabolic equivalent.</p>1<p>Adjusted for age (years, continuous), parity (0, 1, 2, and ≥3), smoking habit status (never vs. ever), menopause (premenopause vs. postmenopause), human papillomavirus infection status (negative vs. positive), alcohol consumption status (never vs. ever), and oral contraceptive use (never vs. ever).</p