title: Multiple human papillomavirus infection with or without type 16 and risk of cervical intraepithelial neoplasia among women with cervical cytological abnormalities.
abstract: OBJECTIVE
  To evaluate the impact of multiple human papillomavirus (HPV) infections on the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in subjects with cervical cytological abnormalities.
  
  
  METHODS
  A cross-sectional study of 3,842 women attending a colposcopy service was carried out. Genotyping of 18 high-risk, seven low-risk, and two undefined-risk HPVs was carried out by the INNO-LiPA genotyping system.
  
  
  RESULTS
  The final colposcopic/pathological diagnoses were as follows: 1,933 (50.3 %) subjects were negative; 1,041 (27.1 %) CIN1; 280 (7.3 %) CIN2; 520 (13.5 %) CIN3; and 68 (1.8 %) invasive cervical cancer. The prevalence of HPV infection was 75.8 % (2,911/3,842), whereas multiple HPVs were detected in 34.5 % of HPV-positive subjects (2,255/3,842). The adjusted risks of CIN3+ in the group with multiple compared to the group with single infection were 2.31 (95 % CI = 1.54-3.47), among HPV16-positive women, and 3.25 (95 % CI = 2.29-4.61, p = 0.21 compared with HPV16-positive subjects), in HPV16-negative subjects. Out of a total of 1,285 subjects with mild lesions, followed up for a median of 16.1 months (interquartile range = 8.9-36.8), the rate of progression to CIN2-3 was 0.6 % (5/541) among subjects negative or with low-risk HPVs, 1.7 % (8/463) among those with single high-risk HPV, and 5 % (14/281, p < 0.001 compared with HPV-negative/low-risk HPV and p = 0.038 compared with single high-risk HPV) among those with multiple high-risk HPVs.
  
  
  CONCLUSIONS
  Among women with cervical cytological abnormalities, infection by multiple high-risk HPVs increased the risk of CIN3+ in both HPV16-positive and HPV16-negative subjects. These findings suggest a potential synergistic interaction between high-risk HPVs, favoring the progression of CIN lesions.
authors.affiliation: Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, University of Pavia, P.le Golgi, 19, 27100, Pavia, Italy, spinillo@smatteo.pv.it.
authors.forename: Arsenio
authors.initials: A
authors.lastname: Spinillo
authors.forename: Barbara
authors.initials: B
authors.lastname: Gardella
authors.forename: Marianna
authors.initials: M
authors.lastname: Roccio
authors.forename: Paola
authors.initials: P
authors.lastname: Alberizzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Cesari
authors.forename: Morbini
authors.initials: M
authors.lastname: Patrizia
authors.forename: Enrico
authors.initials: E
authors.lastname: Silini
mesh_terms: D000328:Adult; D000368:Aged; D003127:Colposcopy; D003430:Cross-Sectional Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology; D016387:Women's Health; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000821:virology