title: Infections with multiple high-risk HPV types are associated with high-grade and persistent low-grade intraepithelial lesions of the cervix.
abstract: BACKGROUND
  Infections with multiple human papillomavirus (HPV) types (mHPV) in Papanicolaou tests have been reported but the histologic correlation and clinical meaning remains debatable.
  
  
  METHODS
  The authors prospectively tested 37 HPV types using the Linear Array HPV Genotyping Test and correlated the results to cytology and histology findings in 260 women evaluated from June 2009 to October 2011 and followed for up to 60 months.
  
  
  RESULTS
  HPV was detected in 148 of 235 samples (63%) and high-risk HPV was detected in 132 samples (56%). mHPV infection was found to be twice as common as single HPV (sHPV) infection and was detected more frequently in low-grade squamous intraepithelial lesion (LSIL) (48 of 83 samples [58%]) and high-grade squamous intraepithelial lesion or invasive carcinoma (HSIL + (26 of 47 samples [55%]) compared with other categories (P<.001). Of 34 LSIL/cervical intraepithelial neoplasia 1 (CIN1) index cases, 13 of 21 patients with mHPV (61.9%) persisted on CIN1, whereas no histologic abnormality was detected during follow-up in all 12 patients with sHPV infection (high risk or low risk) (P<.001). Eighteen of 20 patients with HSIL/cervical intraepithelial neoplasia 2 (CIN2) (90%) and high-risk mHPV persisted on HSIL+/CIN2 + whereas 6 of 11 patients with sHPV infection did not demonstrate HSIL+/CIN2 + on follow-up (54.5%) (P = .066). Approximately 40% of women with HSIL were infected by high-risk HPV types other than types 16 or 18.
  
  
  CONCLUSIONS
  High-risk mHPV infection identified patients with persistent LSIL/CIN1 and may to help identify patients at higher risk of disease progression to HSIL+/CIN2+. Longer follow-up will clarify the role of mHPV testing in patient care. Cancer Cytopathol 2017;125:138-143. © 2016 American Cancer Society.
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Louise
authors.initials: L
authors.lastname: De Brot
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pellegrini
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Sabrina Teixeira
authors.initials: ST
authors.lastname: Moretti
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.affiliation: Department of Gynecology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Victor Piana
authors.initials: VP
authors.lastname: de Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis / Q000473:pathology*
keywords: cervical cancer; coinfection; gynecological cytology; human papillomavirus; human papillomavirus genotyping; intraepithelial lesions