Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Prognostic value of serum creatine level in patients with vulvar cancer.

Vulvar cancer is a rare malignancy with poor prognosis that generally occurs in elderly patients. The individual prognosis is difficult to assess. Serum creatinine levels are frequently elevated in elderly patients. Recent evidence have shown shown that - besides indicating kidney impairment - serum creatinine levels may be used to predict the survival in cancer patients. Several studies observed an association between elevated serum creatinine levels and poor prognosis in patients with solid tumors. In this retrospective cohort study, serum creatinine levels were evaluated in 170 patients with invasive vulvar cancer. Serum creatinine levels were correlated to established clinicopathologic factors. Univariate and multivariate survival analysis were performed. Elevated serum creatinine levels (>1.2 mg/dl) were significantly associated with both poor disease specific and overall survival. Three year overall survival rates were 74.8% and 32.5% for patients with serum creatinine levels of ≤ and >1.2 mg/dl, respectively. In a multivariate survival model, serum creatinine levels were significantly associated with overall survival independent of tumor stage and patients' age. In conclusion, pretherapeutic serum creatinine levels may be useful as an independent prognostic parameter in patients with vulvar cancer.

ABO blood groups as a prognostic factor for recurrence in ovarian and vulvar cancer.

The relationship between ABO blood groups (BG) and risk of incidence in cancers including gynecological cancers has been widely studied, showing increased incidence risk for BG A patients. As available data are inconsistent we investigated whether BG and their anti-glycan antibodies (anti-A and anti-B) have prognostic values in gynecological cancers. We retrospectively evaluated 974 patients with gynecological cancers in three cancer centers (Switzerland and Australia) between 1974 and 2014 regarding the relationships between clinico-pathological findings and the BG. Time to disease recurrence was significantly influenced by BG in patients with ovarian (n = 282) and vulvar (n = 67) cancer. BG O or B patients showed a significantly increased risk for ovarian cancer relapse compared to A, 59% and 82%, respectively (p = 0.045; HR O vs A = 1.59 (CI 1.01-2.51) and (p = 0.036; HR A vs B = 0.55 (CI 0.32-0.96). Median time to relapse for advanced stage (n = 126) ovarian cancer patients was 18.2 months for BG O and 32.2 for A (p = 0.031; HR O vs A = 2.07 (CI 1.07-4.02)). BG also significantly influenced relapse-free survival in patients with vulvar cancer (p = 0.002), with BG O tending to have increased relapse risk compared to A (p = 0.089). Blood groups hence associate with recurrence in ovarian and vulvar cancer: women with BG O seem to have a lower ovarian cancer incidence, however are more likely to relapse earlier. The significance of the BG status as a prognostic value is evident and may be helpful to oncologists in prognosticating disease outcome and selecting the appropriate therapy.

Decreased NK cell activity after partial vulvectomy in pregnant patient with vulvar intraepithelial neoplasia 3 (VIN3).

INTRODUCTION AND OBJECTIVE: The study presents the problem of immune disturbances in pregnant women with vulvar carcinoma in situ (VIN3). MATERIAL AND METHODS: NK cell and T reg activity in the study patient were analysed using flow cytometry. RESULTS: Decreased NK cell activity and but increased T reg activity were observed after vulvectomy, with subsequent successful pregnancy outcome. CONCLUSIONS: Although vulvar cancer may influence immune cell activity, this issue merits further study.

Normalizers for microRNA quantification in plasma of patients with vulvar intraepithelial neoplasia lesions and vulvar carcinoma.

The role of circulating microRNAs as a promising tool for diagnosing cancer and monitoring anticancer therapies has been widely studied in the past decades. To date, no suitable reference microRNAs for normalizing quantitative real-time polymerase chain reaction assays has been identified in vulvar intraepithelial neoplasia lesions and vulvar squamous cell carcinoma. The purpose of this study was to select appropriate references for gene expression studies in plasma of patients with these lesions. Expression levels of six microRNAs-hsa-miR-425-5p, hsa-miR-191-5p, hsa-miR-93-5p, hsa-miR-423-5p, hsa-miR-103a-3p, and hsa-miR-16-5p-were analyzed by quantitative reverse transcription polymerase chain reaction in plasma samples obtained from 17 patients with vulvar intraepithelial neoplasia lesion and 27 patients with vulvar squamous cell carcinoma. The expression stability of these candidate normalizers was assayed using geNorm algorithm. hsa-miR-93-5p was revealed as the most stably expressed reference in plasma samples of both vulvar intraepithelial neoplasia lesion and vulvar squamous cell carcinoma patients. The results pointed at hsa-miR-93-5p and hsa-miR-425-5p as microRNAs that retained the greatest robustness in plasma of vulvar intraepithelial neoplasia lesion and vulvar squamous cell carcinoma patients, respectively. Our work is the first report on reference microRNA selection for quantitative real-time polymerase chain reaction applications in vulvar intraepithelial neoplasia lesion and vulvar squamous cell carcinoma. The candidate microRNA stability values for the two types of lesions are provided and might serve for normalization of the future novel microRNA biomarkers in these rare entities.

Association between hypoalbuminemia and surgical site infection in vulvar cancers.

OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication.

The impact of plasma fibrinogen levels on patients with vulvar cancer.

OBJECTIVE: To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters. STUDY DESIGN: In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients' survival. RESULTS: Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p=0.001), lymph node involvement (pN0 vs. pN1, p=0.04), and histological grade (G1 vs. G2 vs. G3, p=0.03), but not with patients' age (≤ 70 years vs. >70 years, p=0.6). In a multivariate survival analysis, tumor stage (p=0.006/p=0.02) and lymph node involvement (p<0.001/p<0.001), but neither histological grade (p=0.2/p=0.9) nor plasma fibrinogen levels (p=0.6/p=0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤ 70 years vs. >70 years) was associated with overall survival (p=0.03) but not with disease-free survival (p=0.1). CONCLUSION: Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.

Serum 25-hydroxyvitamin D levels in patients with vulvar cancer.

BACKGROUND: The anticarcinogenic potential of vitamin D 25(OH)D has been attributed to the inhibition of proliferation of cells from different carcinomas. Reduced serum levels of 25(OH)D are associated with an increased incidence of various types of cancer. The influence of serum 25(OH)D on the incidence and outcome of patients with vulvar cancer is unknown. PATIENTS AND METHODS: The serum 25(OH)D levels in 24 patients with vulvar cancer and 24 age-matched cancer-free patients was investigated. The blood samples were collected between October 2009 and September 2010 and time of blood collection of each patient and control was matched to avoid seasonal variations between the pairs. RESULTS: The median 25(OH)D serum levels in the under 50 year old group of patients were significantly lower in the vulvar cancer group than the controls. The younger cancer group also had an age-related trend of lower median serum level than the older population. In the control population the trend was vice versa, yet this finding was not statistically significant. CONCLUSION: Serum 25(OH)D has a possible role in the pathogenesis and progression of vulvar cancer, but further investigations of the association of vitamin D and vulvar cancer as well as regarding its influence on patient survival and quality of life are warranted in the future.

[Characteristics of anemia in patients with oncogynecological pathology].

The aim of the study was to elucidate complex changes in Hgb, erythrocyte count, ESR, and MCH in patients with oncogynecological problems depending on the affected organ and stage of the disease. A total of 340 women were examined in the oncogynecological department of No 40 city hospital, Moscow, from 2005 to 2008. The group included 132 patients with gynecological, 177 with oncogynecological and 31 with oncologycal diseases. A common coefficient was derived to characterize functional activity of erythrocytes The notion of intoxication effect coefficient (IC) is introduced and substantiated. Erythrocyte IC is shown to be useful for the comparison of groups with gynecological and oncogynecological problems. It decreases in patients with a tumorigenic process depending on its phase.

[Comparative analysis of erythrocytic indices in patients with gynecological diseases and gynecological neoplasms].

The study enrolled 177 women with gynecological cancer and 132 with gynecological disease. Hemoglobin (Hb), mean corpuscular hemoglobin (MCH), red blood cells (RBC), and erythrocyte sedimentation rate (ESR) were analyzed. The gynecological patients with anemia showed a correlation between Hb and MCH (p < 0,05), which is indicative of iron deficiency. In the gynecological cancer patients, the correlation between Hb and MCH was significant (p < 0,01), that between Hb and RBC was strong (p < 0,001), suggesting the reductions in both erythropoiesis and Hb synthesis in the erythrokaryocytes. In these patients, anemia results from chronic diseases. The gynecological cancer patients were found to have higher ESR and lower Hb, RBC, and MCH than the gynecological patients.

The inflammation-based modified Glasgow Prognostic Score in patients with vulvar cancer.

OBJECTIVES: To evaluate the prognostic potential of the modified Glasgow Prognostic Score (mGPS), known to reflect the degree of tumor-associated inflammation and cachexia, in patients with vulvar cancer. STUDY DESIGN: We included 93 consecutive patients with vulvar cancer into our study. As previously published, the pre-therapeutic mGPS was calculated as follows: patients with elevated C-reactive protein (CRP) serum levels (>10 mg/L) and hypoalbuminaemia (<35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminaemia were allocated a score of 1, patients with normal CRP serum levels with or without hypoalbuminaemia were allocated a score of 0. The mGPS was correlated with clinico-pathological parameters. The association between mGPS and prognosis was evaluated by univariate and multivariate survival analysis. RESULTS: Mean (SD) pretreatment CRP and albumin serum levels were 9.5 (9.6) mg/L and 41.4 (5.3) g/L, respectively. mGPS was associated with tumor stage (p=0.01), but not with lymph node involvement (p=0.4), histological grade (p=0.8), and patients' age (p=0.7). In univariate analyses, mGPS (p=0.006, p=0.001), tumor stage (p<0.001, p<0.001), lymph node involvement (p<0.001, p<0.001), and patients' age (p=0.04, p=0.007), but not histological grade (p=0.1, p=0.3) and year of surgery (1995-2001 vs. 2002-2008, p=0.7, p=0.3) were associated with disease-free and overall survival, respectively. In a multivariate analysis, tumor stage (p=0.01, p=0.02) and lymph node involvement (p<0.001, p=0.001), but not mGPS (p=0.7, p=0.8), patients' age (p=0.6, p=0.4), histological grade (p=0.2, p=0.1), and year of surgery (p=0.4, p=0.8) were associated with disease-free and overall survival, respectively. CONCLUSIONS: Despite being associated with prognosis in a univariate analysis, mGPS cannot be used as an independent inflammation-based predictor for survival in patients with vulvar cancer.

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.

C-reactive protein serum levels are closely associated with lymph node status, but not with prognosis in patients with vulvar cancer.

OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels can be used as prognostic parameter in patients with vulvar cancer. STUDY DESIGN: CRP serum levels were measured at the time of first diagnosis of squamous cell vulvar cancer. Sixty-seven patients were enrolled; results were correlated to clinical data. RESULTS: Mean CRP serum levels in patients with vulvar cancer were 0.8 (0.80)mg/dL. CRP serum levels were significantly associated with lymph node involvement (p=0.003), but not with tumor stage (p=0.03), histological grade (p=0.86) and patients' age (p=0.64). Univariate analysis showed lymph node involvement, tumor stage and histological grade, but not CRP serum levels and patients' age to be associated with overall survival. A multivariable analysis determined only lymph node involvement as independent prognostic parameter for disease-free interval and overall survival. CONCLUSION: CRP serum levels are closely associated with lymph node status but cannot be used as prognostic parameter in patients with vulvar cancer.

Association between invasive squamous cell carcinoma of the vulva and ABO blood group.

OBJECTIVE: To determine whether the distribution of ABO blood group among women with invasive squamous cell carcinoma (SCC) of the vulva is different from that among a population of women treated for nonneoplastic gynecologic disease. METHODS: A retrospective analysis of pathology reports and blood bank records from January 1996 through September 2003 was performed. The distribution of ABO blood group for 33 women diagnosed with invasive SCC of the vulva was determined. ABO blood group was also recorded for 100 female patients (controls) who underwent a gynecologic procedure for a nonneoplastic process during the period January 2003 through November 2003. The blood group phenotype distribution for the study groups and the controls was compared by an incidence ratio. RESULTS: Statistical analysis gave an incidence ratio for blood group types A and O of 1.55 (p < .20) when the patients with invasive SCC of the vulva were compared with the controls. The p value was not significant. Similarly, the incidence ratio for blood group types B and O equaled 0.386 (p = 1). Again the p value was not significant. In fact, none of the incidence ratios calculated were statistically significant. Although not statistically significant, the incidence ratio for the invasive vulvar SCC group was >1. This may indicate that there is a trend for women with invasive SCC of the vulva to have blood group type A. CONCLUSIONS: Results of this study do not suggest an association between blood group type A, or any other blood group, and vulvar SCC. This study was similar in patient size to another study (33 patients with vulvar SCC vs. 39 patients with vulvar SCC, respectively). The disparity of the results in determining the significance of blood group type A as an associated factor for vulvar SCC in this and the other study may be due to the limited size of the study populations. Additional investigation is needed to further evaluate this issue.

Serum levels of squamous cell carcinoma antigen as a predictor of inguinofemoral lymph node metastasis in patients with vulvar cancer.

OBJECTIVE: To evaluate the predictive value of preoperatively determined squamous cell carcinoma antigen (SCC-Ag) serum levels for the risk of inguinofemoral lymph node metastasis. STUDY DESIGN: In this retrospective trial, preoperative serum levels of SCC-Ag in 29 patients with invasive squamous cell vulvar cancer (pT1 + 2) were evaluated and compared with nodal status. RESULTS: Twenty patients had negative inguinofemoral nodes, whereas in nine an inguinofemoral lymph node metastasis could be observed. The median SCC-Ag in women with negative nodes was 1.3 micrograms/L (0.2-11.5) and with positive nodes, 2.7 micrograms/L (0.4-9.1) (P = .35). CONCLUSION: Measurement of the serum level of SCC-Ag cannot be used for preoperative evaluation of the risk of lymph node metastasis in patients with clinically localized tumors since there is a significant overlap between both cohorts.

Is there a link between vulval cancer and blood group?

Risk factors for squamous cell vulval cancer (SCC) remain unclear though there have been associations with lichen sclerosis, smoking, and vulval intraepithelial neoplasia (VIN). We studied 191 patients who had been referred to the vulval clinic at the Royal Free Hospital and who had both blood group and histopathology results available. Seventy-two percent of patients with SCC and non-neoplastic epithelial disorders of the vulva (NNEDV) were found to be in blood group A with only 17% in blood group O. Those with SCC associated with VIN had only 30% in blood group A with 50% in blood group O. The control population showed that 38% of the population were in blood group A and 43% were in blood group O. Our results suggest that blood group A is prevalent in patients with SCC associated with NNEDV but not in those women with squamous vulval cancer and associated VIN.

Stage-related superoxide anion production of granulocytes of gynecologic cancer patients.

OBJECTIVE: To measure superoxide anion production of polymorphonuclear leukocytes (PMNLs) in 58 gynecologic cancer patients and compare to that of healthy controls. METHODS: PMNLs were separated from peripheral blood samples by Ficoll and subsequent Percoll gradient sedimentation. Baseline and phorbol-dibutyrate (100 nmol/l) stimulated superoxide anion production was measured spectrophotometrically as superoxide dismutase inhibitable reduction of ferricytochrome c (50 micromol/l) absorbance. Differences between the mean superoxide anion production of different patient groups and the control group were assessed by Student's t-test. RESULTS: The mean superoxide anion production of PMNLs of healthy controls was 1.855 nM/min/3 x 10(5) cells (SD=0.211 nM/min/3 x 10(5) cells). Superoxide anion production of gynecologic cancer patients and healthy controls varied in a wide range. PMNLs of patients had lower baseline and stimulated activity than those of healthy volunteers. The frequency of a mean superoxide production at least 2 x SD below the control showed a parallel increase with advancing stage. CONCLUSION: Granulocytes of gynecologic cancer patients have reduced capacity and inducibility of superoxide anion production already at an early stage of disease.