Distribution of HPV Subtypes in Diverse Anogenital and Oral Samples from Women and Correlation of Infections with Neoplasia of the Cervix

Background: Cancers and intraepithelial lesions of different anogenital areas as well as oral cancer are associated with human papilloma virus (HPV) infections. Methods: In this study cervical, vaginal, vulvar, anal, and oral samples were taken from 509 patients visiting our dysplasia consultation clinic. HPV genotyping was performed using the EUROArray HPV test. Results: Positivity of HR HPV was found in 60.4–64.3% of anogenital and 14.6% of oral samples. HPV 16 showed the highest incidence in all investigated areas. In cervical and vaginal samples HPV 31 was detected second most, while in vulvar, anal, and oral samples HPV 53 was the second most common subtype. HPV 18 was found lower in all areas, while HPV 51, HPV 52, and HPV 73 were detected higher than expected from published data. A good concordance between cervical, vaginal and vulvar samples was examined for most of the HPV. HR HPV infection was higher in cervical cancer (CC; 91.7%) and high-grade intraepithelial squamous lesions (HSIL; 93.9%) compared to low-grade SIL (LSIL; 69.6%) and normal samples (44.8%). Conclusion: In addition to the well described HPV subtypes, we found others with high incidences in the investigated areas which may be evident for HSIL and CC of those areas

L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.

BACKGROUND/AIMS: The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. METHODS AND RESULTS: Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). CONCLUSIONS: Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models

The proliferative status of endometriotic cells in the induced endometriotic lesions assessed by PCNA immunostaining.

<p>Negative and positive (breast cancer) controls were included to determine the specificity of the immunostainings (magnification: x100 and x200).</p

Identification and analysis of induced endometriotic lesions.

<p>(A) Four weeks after treatment, B6C3F1 (I, II) and CD-1 nude (III, IV) mice were sacrificed; endometrial implants were identified (black arrows) and excised for further analysis. Adhesions were also observed at implant sites in the B6C3F1 (II) and CD-1 (IV) mice and involved the liver (<i>L</i>) and gut (<i>G</i>). (B) Hematoxylin-eosin staining of the endometriotic tissues derived from both mouse groups was performed for histological evaluation (magnification: x100). (C) The presence of L1CAM was observed in the endometriotic implants derived from autologous (I) and heterologous (II) models by immunohistochemistry. Negative (III) and positive (colon, squamous epithelium) (IV) controls are shown (magnification: x200).</p

Endometriosis mouse models.

<p>(A) <i>In </i><i>vivo</i> magnetic resonance imaging (MRI), fat saturated T2-weighted Turbo spin echo images using a dedicated wrist coil at 3T: The red arrows indicate one experimentally induced-endometriotic implant in B6C3F1 and CD-1 nude mice. In a set of B6C3F1 mice, MRI was performed before and after antibody treatment. (B) Laparotomies performed in the CD-1 nude mice 4 (I, II) and 8 (III-V) weeks after the implantation; the black arrows denote the development of two peritoneal endometrial transplants that are shown indicated with arrows in images IV and V after peritoneal layer disruption. (C) Effect of endometrial tissue inoculation and treatment with anti-L1 mAb and control-antibody on body weight.</p