title: Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer.
abstract: OBJECTIVE
  The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk.
  
  
  METHODS
  HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination.
  
  
  RESULTS
  In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone.
  
  
  CONCLUSIONS
  These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL.
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
authors: Adela
authors: A
authors: Carrillo-García
authors: Unidad de Epidemiología Clínica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán INCMNSZ, México D.F. 14000, Mexico.
authors: Sergio
authors: S
authors: Ponce-de-León-Rosales
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
authors: David
authors: D
authors: Cantú-de-León
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
authors: Verónica
authors: V
authors: Fragoso-Ontiveros
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
authors: Imelda
authors: I
authors: Martínez-Ramírez
authors: Dirección General Adjunta de Sanidad Naval, Secretaría de Marina, México D.F. 04830, Mexico.
authors: Asunción
authors: A
authors: Orozco-Colín
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
authors: Alejandro
authors: A
authors: Mohar
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico. Electronic address: lizano@unam.mx.
authors: Marcela
authors: M
authors: Lizano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060085:Coinfection / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*
keywords: HPV coinfections; HSIL; Invasive cervical cancer; LSIL; NILM