title: Detection of Human Papillomavirus Infection in Patients with Vaginal Intraepithelial Neoplasia.
abstract: BACKGROUND
  Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.
  
  
  METHODS
  67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System).
  
  
  RESULTS
  All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn't be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.
  
  
  CONCLUSIONS
  HPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse.
authors.affiliation: Department of Dermatology, Ludwigshafen Hospital, Ludwigshafen, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lamos
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mihaljevic
authors.affiliation: Practice for Pathology, Frankfurt, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Domschke
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Paringer
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Fluhr
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Dinkic
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Brucker
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Golatta
authors.affiliation: University of Vienna, Vienna, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gensthaler
authors.affiliation: Department of Gynecology and Obstetrics, Helios Dr. Horst Schmidt Kliniken, Wiesbaden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Eichbaum
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rom
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012307:Risk Factors; D014621:Vagina / Q000473:pathology / Q000821:virology; D014625:Vaginal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology