The high-risk human papillomavirus continuum along the female reproductive tract and its relationship to infertility and endometriosis.

RESEARCH QUESTION: Is there an association between the presence of sexually transmitted pathogens in the lower (LGT) and upper (UGT) female genital tract with endometriosis and infertility? DESIGN: Case-control study with 60 women submitted to gynaecological laparoscopic surgery. Samples from the UGT and LGT were collected and analysed by single polymerase chain reaction (PCR) for human papillomavirus (HPV) and by multiplex PCR for other sexually transmitted infections (STI). Patients were initially divided into two clinical groups: infertile patients (n = 25) with conjugal infertility and fertile control patients (n = 35). After the surgical findings patients were further divided for additional analysis: an endometriosis group (n = 29) and non-endometriosis control group (n = 31). RESULTS: Sixty per cent of patients were positive for DNA-HPV in some of the genital tract sites sampled. Infertile patients were associated with high-risk HPV (hrHPV) positivity in the UGT sites (P = 0.027). The endometriosis group was associated with hrHPV positivity in the LGT and UGT sites (P = 0.0002 and P = 0.03, respectively). Only hrHPV types were detected in the UGT in both groups. It may be that there is a hrHPV infection continuum, from LGT to UGT, in infertile and endometriosis patients. No association was observed among the other seven STI studied. CONCLUSIONS: This study shows both an association between hrHPV infections in the UGT with infertility and endometriosis, and a possible hrHPV infection continuum, from LGT to UGT. Larger studies are needed to fully investigate the role of hrHPV as a cause of endometriosis and infertility.

Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis.

AIM: In this study, we aimed to determine the prevalence of human papillomavirus (HPV) in ovarian endometriosis and ovarian tissue from women without endometriosis. Understanding the pathogenesis of the disease could help us design preventative strategies as well as novel and appropriate treatment approaches in this regard. METHODS: In this cross-sectional study, formalin-fixed and paraffin-embedded tissue sections from 50 and 49 ovaries with and without endometriosis, respectively, were evaluated for the presence of high-risk HPV using the polymerase chain reaction technique. Prevalence of HPV infection and other related characteristics of the studied population were compared. RESULTS: High-risk HPV infection was detected in 13 (26%) and five (10.2%) of the samples with and without endometriosis, respectively (P = 0.041, χ2  = 3.16). Mean age and parity were not significantly different in subjects with and without HPV infection in the two studied groups (P = 0.7 and P = 0.06 for age in case and control groups, respectively; and P = 0.32 and P = 0.09 for parity in case and control groups, respectively). CONCLUSION: The results of our study indicated a higher rate of high-risk HPV infection among patients with endometriosis. The findings could provide us baseline information for future studies regarding the pathogenesis of endometriosis and the role of viral infection and their possible impact on future cancer development in this group of patients.

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

Low prevalence of DNA viruses in the human endometrium and endometriosis.

The chronic female disease endometriosis causes debilitating pain and lowered fertility. The aetiology is unknown, but indications of an infectious agent are present. This study investigates the possible involvement of a pathogenic virus in endometriosis patients and controls. DNA was purified from biopsies and subjected to highly sensitive PCR tests detecting human papillomavirus (HPV) types, the herpes family viruses HSV-1 and -2, CMV, and EBV, and the polyomaviruses SV40, JCV, BKV, KIV, WUV, and MCV. The prevalence of pathogenic DNA viruses in the human endometrium was generally low (0-10%). The virus prevalence was found to vary slightly when comparing the endometrium of healthy women and women with endometriosis. However, these were not significant differences, and no viruses were identified in endometriotic lesions. These results do not point towards any evidence that endometriosis is caused by these viruses.

Treatment of endometriosis with a VEGF-targeted conditionally replicative adenovirus.

OBJECTIVE: To evaluate a vascular endothelial growth factor (VEGF)-targeted gene therapy for the treatment of endometriosis. DESIGN: Analysis of the VEGF gene expression and promoter activity in ectopic and eutopic endometrium. Evaluation of the specific replication and cell-killing effect of a VEGF-targeted adenovirus (Ad5VEGFE1) in endometriotic cells. PATIENT(S): Four patients who underwent hysterectomy for benign disease, 30 women with moderate superficial, and 30 women with deep infiltrating endometriosis. INTERVENTION(S): Immunostaining and gene expression of VEGF was examined in eutopic endometrium, endometriotic lesions, and normal peritoneum. The VEGF promoter activity was evaluated in eutopic endometrium and endometriotic lesions. A VEGF-targeted conditionally replicative adenovirus (Ad5VEGFE1) was evaluated regarding specific viral replication in endometriosis cells and induction of apoptosis. The biodistribution of the VEGF-targeted conditionally replicative adenovirus was examined in a mouse model. RESULT(S): The VEGF gene was highly expressed in ectopic endometrium compared with eutopic endometrium and normal peritoneum. The VEGF promoter was active in endometriotic cells. Ad5VEGFE1 showed efficient viral replication and induction of apoptosis in purified primary endometriotic cells and demonstrated a similar lower targeting to the liver and the uterus in a mouse model. CONCLUSION(S): Ad5VEGFE1 is a promising candidate for treating endometriosis and holds potential for clinical testing.

Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions.

OBJECTIVE: To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis, are associated with endometriosis lesions. DESIGN: Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction-based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. SETTING: University hospital. PATIENT(S): Seventy individual patients with and without endometriosis. INTERVENTION(S): Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. RESULT(S): Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. CONCLUSION(S): HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.

Endometriosis mimicking ovarian cancer in the setting of acquired immune deficiency syndrome.

BACKGROUND: With rising rates of human immunodeficiency virus (HIV) among women and resultant immunosuppression, clinicians face varying presentations of gynecologic pathologies. We report a case of endometriosis in a patient with acquired immunodeficiency syndrome (AIDS) presenting with a Sister Mary Joseph's nodule and mimicking carcinomatosis. CASE: A woman with AIDS and 2-month history of abdominal pain, distention, and weight loss was found to have periumbilical and pelvic masses, ascites, lymphadenopathy, and an elevated CA 125 level. Operative findings included chocolate-colored ascites and peritoneal seeding involving the ovaries, uterus, appendix, bowel, umbilicus, and omentum. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and resection of all gross disease. Pathologic diagnosis was endometriosis and AIDS-associated adenopathy. COMMENT: Immunodeficiency from AIDS can affect the progression of endometriosis to the point of mimicking ovarian malignancy.

Physiological and cytogenetic characterization of immortalized human endometriotic cells containing episomal simian virus 40 DNA.

The study of misplaced endometrial cells, which abnormally implant and grow outside the uterine cavity, is of considerable interest for the understanding of the pathophysiology of endometriosis. However, endometriotic cells, particularly epithelial cells, required for primary cell culture are not easily available. We report here the characterization of an endometriotic cell line immortalized after infection of primary endometriotic cell cultures with simian virus 40. Transformed cells express T-antigen, and blot hybridization analysis showed that the viral genome is present as an episome. Cytogenetic analysis revealed a polyploid karyotype with numerical and structural rearrangements involving mainly the same chromosomes (6, 10, 11, 15, and 17). The cell line has been maintained in culture for over 80 passages and was still proliferating without any noticeable change in the biological properties investigated. Transformed endometriotic cells expressed both progesterone and estradiol receptors and were stimulated by these ovarian hormones to secrete monocyte chemotactic protein-1, a factor that may play an important role in the recruitment and activation of peritoneal macrophages. In addition, this response was enhanced in interleukin-1-treated cells. Taken together, these findings support the view that this cell line may be an interesting tool for the study of the pathophysiology of endometriosis.