Negative HPV testing among patients with biopsy-proven cervical intraepithelial neoplasia grade 2/3 or cervical cancer.

OBJECTIVE: To determine the proportion of patients diagnosed with cervical cancer or cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3) despite testing negative for HPV. METHODS: A prospective study was conducted at a university hospital in Barcelona, Spain, between March 2003 and January 2015 among women with abnormal cytology results according to the Bethesda classification system. All participants underwent HPV testing, cytology, and colposcopy. RESULTS: Among 1376 participants, 609 (44.3%) were diagnosed with CIN 2/3. Of these women, 74 (12.2%) tested negative for HPV. Among 479 women with colposcopy-guided biopsy sampling showing CIN 2/3, cone biopsy results that were negative for CIN 2/3 were more frequent among patients with negative HPV testing (13/61 [21.3%]) than among those with positive HPV tests (58/418 [13.9%]; P=0.03). Additionally, among 59 patients diagnosed with cervical cancer, 9 (15.3%) tested negative for HPV. CONCLUSION: The HPV test was negative for 12% and 15% of patients diagnosed with biopsy-proven CIN 2/3 and cervical cancer, respectively.

Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2-3).

OBJECTIVE: To identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2-3). METHODS: Prospective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis. RESULTS: HPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p=0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types. CONCLUSION: Only 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.

Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia.

OBJECTIVES: (a) To establish the reference values for plasma total homocysteine in our pregnant population. (b) To determine the possible association between hyperhomocysteinemia and preeclampsia in our geographical area. STUDY DESIGN: Control-case study with 32 preeclamptic patients and 64 controls without pregnancy complications. Plasma total homocysteine, determined by HPLC (fluorescence detection), was correlated with serum folate and Vitamin B(12) (analyzed by competitive protein binding chemiluminescent assay). STATISTICAL ANALYSES: Mann-Whitney, Wilcoxon and Spearman test (SPSS, 10.0). RESULTS: Homocysteine concentrations in the controls were significantly higher while folate was significantly lower in the third trimester of pregnancy when compared with the second (P<0.0001). Homocysteine and folate values were significantly higher in patients compared with controls in the third trimester (P=0.005 and 0.005, respectively). The OR for preeclampsia in hyperhomocysteinemia was 7.7 (95% CI: 1.7-34.8). CONCLUSION: Pregnant women with hyperhomocysteinemia have a 7.7-fold risk for preeclampsia (CI 95%: 1.7-34.8) compared with normal controls.

Inhibin and follicular development in heterotopical ovary transplants without vascular pedicle in syngeneic Lewis rats.

OBJECTIVE: To evaluate the role of inhibin in elevated base levels of FSH and follicular hyperplasia in ovarian autotransplantation in rats. DESIGN: Experimental animal study. SETTING: Unit of Experimental Research at the Barcelona University School of Medicine. ANIMAL(S): Female syngeneic Lewis rats aged 16 weeks. INTERVENTION(S): The animals were randomized into two groups: group A, control group undergoing only laparotomy (n = 5) and group B, oophorectomized with SC autologous heterotopic transplant (n = 5). The animals were killed and their ovaries removed for histologic, morphometric, and immunohistochemical analysis at 28 days after surgery in both groups. MAIN OUTCOME MEASURE(S): Serum levels of E2 and FSH were determined on day 0 (the day of surgery or baseline) and days 4, 7, 14, 21, and 28. Morphometric analysis of ovarian structure for evaluation of antral follicles and their granulosa cell area and immunohistochemistry for inhibin staining were also done. RESULT(S): The endocrinological function recovered at 28 days, and the FSH levels for the transplant group were significantly higher than for the group with normoinsert ovary. Morphometric analysis showed that the mean granulosa cell area was greater in group B when compared with the control group. Immunohistochemistry revealed almost null inhibin staining of the stroma in transplanted ovarian tissue. CONCLUSION(S): Tissue damage brought on by ischemia in the transplant of nonvascularized ovaries may bring about an inhibin deficit in the ovarian stroma, which might explain the increased levels of FSH. These increased levels, in turn, would be responsible for the follicular hyperplasia seen in this tissue when it recovers its function.

Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis rats: long-term evaluation of effects on ovarian structure and function.

OBJECTIVE: To assess the long-term efficacy of intraperitoneal (IP) and subcutaneous (SC) ovarian autotransplantation in rats. DESIGN: Experimental animal study. SETTING: Unit of Experimental Research, Barcelona University School of Medicine. ANIMAL(S): Female syngeneic Lewis rats aged 14 weeks. INTERVENTION(S): Group A, control group undergoing ovariectomy (n = 15); group B, undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In groups B and C, five animals were killed and their ovaries removed for morphometric analysis at 30 days after transplantation; five additional animals were killed at 180 days, and the remaining five animals were killed at 360 days. MAIN OUTCOME MEASURE(S): Ovarian morphometric analysis and serial measurement of E(2) and FSH serum levels. RESULT(S); The mean number of antral follicles in the control group A was significantly higher than that observed in the ovarian grafts collected and examined 30 days after grafting in rats from groups B and C, but the mean granulosa cell area was significantly higher in both transplantation groups than in controls because of ovarian follicular hyperplasia. Histological examination of ovaries removed at 6 and 12 months after grafting in groups B and C showed increasing degrees of fibrosis, loss of primordial follicles, and the presence of epithelial cysts. In groups B and C, from day 30 after surgery onward, serum E(2) was significantly higher and FSH significantly lower, respectively, than in group A. E(2) and FSH patterns in groups B and C were similar throughout the study period. CONCLUSION(S): Heterotopic ovarian transplantation without vascular pedicle in rats is characterized by follicular hyperplasia endocrinologically functional, followed by progressive loss of follicles in heterotopic ovarian autografts.