History of HPV in HPV-positive elderly women.

Background: The aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. Methods: Eighty-nine women aged 60-82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999. Results: Of the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative. Conclusion: Surprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.

Incidence of oncogenic HPV and HPV-related dysplasia five years after a negative HPV test by self-sampling in elderly women.

PURPOSE: Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative. METHODS: Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology. RESULTS: Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology. CONCLUSION: The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.

Borrelia Ocular Infection: A Case Report and a Systematic Review of Published Cases.

INTRODUCTION: Lyme borreliosis can cause many diverse manifestations, also ocular disease where the diagnosis of ocular borreliosis is challenging. The primary aim was to report on the evidence of Borrelia spirochetes in the ocular tissue in presumed ocular borreliosis. METHODS: A systematic review of pathological eye conditions was performed where Borrelia has been suspected in relevant ocular tissue, together with a case report of diagnosed uveitis with polymerase chain reaction (PCR)-confirmed Borrelia afzelii in the vitreous. The evidence for clinical and laboratory diagnosis was evaluated systematically. As a secondary aim, the treatment of ocular Borrelia infection was also evaluated for confirmed cases. RESULTS: Thirteen includable studies were found, and after the removal of case duplicates, eleven unique cases were extracted. Apart from the present case report, 4 other cases reported strong evidence for the detection of B. spirochetes in ocular tissue. Four cases presented reasonable evidence for assumed detected Borrelia, while three additional cases showed only weak diagnostic credibility that Borrelia was detected. CONCLUSION: This systematic review, including all reported cases and our case report, supports evidence of ocular infection of Borrelia species. Furthermore, in case of suspicion of infection and seronegativity, it is justified to look for Borrelia in eye tissue samples. In addition, microscopy without using PCR is not sufficient to confirm the diagnosis of borreliosis on ocular tissue. In the articles studied, there was no unambiguous recommendation of treatment.

HPV prevalence and HPV-related dysplasia in elderly women.

INTRODUCTION: In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above. PATIENTS AND METHODS: From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained. RESULTS: The prevalence of HPV was 4.1%, (95%CI 3.0-5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95%CI 1.7-3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2-0.4%, 18 CIN 1-1.7%). HPV-related dysplasia was found in 2.1%, (95%CI 1.3-3.2, n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected. CONCLUSION: A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.

LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix.

BACKGROUND: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. MATERIALS AND METHODS: LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. RESULTS: In early-stage squamous cell carcinoma (stages IB-IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07-0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09-0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. DISCUSSION AND CONCLUSION: LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.

Discrepancies in expression and prognostic value of tumor markers in adenocarcinoma and squamous cell carcinoma in cervical cancer.

The expression of 11 tumor markers in 129 women with squamous cell compared to 31 women with adenomatous cervical cancer was investigated to detect differences in expression. There was a significantly higher expression of p53, CD4, epidermal growth factor receptor (EGFR), CD44 and stratifin in squamous cell, compared to adenocarcinoma, while there was a higher expression of c-myc in adenocarcinoma. P-53, cyclooxygenase-2 (Cox-2) and c-myc significantly correlated to prognosis in squamous cell carcinoma, but none of the 11 investigated tumor markers had any prognostic value in adenocarcinomas. The prognostic value of individual tumor markers differs with the histological subtype in cervical cancer.

Associations between ten biological tumor markers in squamous cell cervical cancer and serum estradiol, serum progesterone and smoking.

BACKGROUND AND AIM: To study possible associations between selected tumor markers and co-factors in squamous cell cervical cancer. MATERIALS AND METHODS: Ten biological tumor markers representing different functions in carcinogenesis were diagnosed in 128 cases of squamous cell cervical cancer. These were p53, c-myc, EGFR, COX-2, CD4+, VEGF, E-cadherin, CD44, Ki-67 (MIB-1), and p27. Smoking habits and previous oral contraceptive use were registered. Serum estradiol and progesterone levels were evaluated in 80 women. Each marker was compared to these four variables. RESULTS: Highly significant assocations were found between strong c-myc staining (> or = 50%) and increased serum progesterone (p = 0.01), a low EGFR staining (< 20%) and high serum estradiol (p = 0.0007), and an absence of p53 staining and smoking (p = 0.008). There was a association between the absence of p53 and high serum progesterone (p = 0.046). CONCLUSION: The study supports a role of progesterone as a promoter of cervical cancer and indicates that smoking is associated with tumor development.

Predicting the outcome of squamous cell carcinoma of the uterine cervix using combinations of individual tumor marker expressions.

AIM: To evaluate if combining the individual expression patterns of biomarkers targeting different molecular alterations in tumor development will improve prognosis prediction in invasive squamous cell carcinoma of the uterine cervix. PATIENTS AND METHODS: Ten-year follow-up results in 128 women with cervical cancer were compared to the expression of 10 relevant tumor markers, assessed with immunohistochemistry. The markers were selected to represent cell proliferation, tumor suppression, cell-cell adhesion, angiogenesis, apoptosis, inflammation and immune response. All analyses were adjusted for stage. RESULTS: p53 expression, and low expression of c-myc and COX-2 correlated significantly with survival. In addition CD4+ expression was included in the analyses of combinations. When these four tumor markers were combined, two-by-two, ten combinations correlated significantly with 10-year survival. The overall 10-year survival rate with a low COX-2 and a high CD4+ expression was 76% versus 53% in the remaining women (odds ratio 3.73, 95% CI 1.42-11.0). The survival rate with absent p53 and high COX-2 expression in the tumors was 42% versus 71% (odds ratio 0.25, 95% CI 0.10-0.37), while the corresponding figures for the combination of high COX-2 intensity and expression of c-myc were 27% versus 62% (odds ratio 0.13, 95% CI 0.02-0.52). None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did. CONCLUSION: Combinations of selected, biologically plausible tumor markers might be more useful for predicting the outcome than using single markers.

Correlation between serum estradiol/progesterone ratio and survival length in invasive squamous cell cervical cancer.

BACKGROUND: There is epidemiological and laboratory evidence for an association between invasive squamous cell cervical cancer and female sex steroid hormones, such as oral contraceptives. MATERIALS AND METHODS: Premenopausal (n = 72) and postmenopausal (n=118) women with invasive squamous epithelial cervical cancer were included in this study. Serum estradiol and progesterone and DNA S-phase fraction as a measure of proliferative activity were analysed, in 51 pre-, and 77 postmenopausal women, among whom 13 and 43, respectively, died from disease. RESULTS: There was a significant positive correlation between a low serum estradiol/progesterone ratio and short survival in those premenopausal women who eventually died from cancer (p=0.02). Clinical stage was similar when the estradiol/progesterone ratio was dichotomized. There was no association between estradiol/progesterone ratio and survival-months in postmenopausal women. In both pre- and postmenopausal women deceased from cervical cancer, a S-phase fraction at or above 12% was correlated with reduced survival-months (p=0.03). CONCLUSION: These results, if confirmed, contribute to bridging the gap between previous epidemiological and laboratory findings of an association between female sex steroid hormones and squamous cell cervical cancer.