Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial.
BACKGROUND
More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer.


METHODS
The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models.


RESULTS
A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development.


CONCLUSIONS
More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation.


BACKGROUND
clinicaltrials.gov: NCT00122681 .
Unit of Infections and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO), IDIBELL, CIBER-ESP, L'Hospitalet de Llobregat, Avda. Gran via 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. xcastellsague@iconcologia.net.
Xavier
X
Castellsagué
Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki, Finland. Jorma.Paavonen@hus.fi.
Jorma
J
Paavonen
Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.unnop@yahoo.com.
Unnop
U
Jaisamrarn
Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. CWheeler@salud.unm.edu.
Cosette M
CM
Wheeler
Vaccines Trials Group, Telethon Institute for Child Health Research, Perth, WA and Sydney University Discipline of Paediatrics and Child Health, Children's Hospital Westmead, Sydney, NSW, Australia. rachels5@chw.edu.au.
S Rachel
SR
Skinner
University of Tampere, School of Public Health, Tampere, Finland. matti.lehtinen@uta.fi.
Matti
M
Lehtinen
Hospital de Clínicas de Porto Alegre, Department of Gynecology & Obstetrics Federal University of Rio Grande do Sul - UFRGS/HCPA, Porto Alegre, Brazil. cacontrol@hcpa.ufrgs.br.
Paulo
P
Naud
Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan. snchow@ntu.edu.tw.
Song-Nan
SN
Chow
San Pablo Colleges Medical Center, San Pablo City, Laguna, Philippines. runnymeadow@yahoo.com.
Maria Rowena
MR
Del Rosario-Raymundo
Departamento de Tocoginecologia da Unicamp, University of Campinas, Campinas, Sao Paulo, Brazil. juliotex@uol.com.br.
Julio C
JC
Teixeira
Central Hospital of North Carelian, Department of Obstetrics and Gynecology, Joensuu, Finland. johanna.palmroth@dnainternet.net.
Johanna
J
Palmroth
Department of Gynecology and Obstetrics, Federal University of Paraná, Infectious Diseases in Gynecology and Obstetrics Sector, Curitiba, Parana, Brazil. infectogin@ufpr.br.
Newton S
NS
de Carvalho
Department of Obstetrics and Gynaecology, University of the Philippines College of Medicine, Philippines General Hospital, Manila, Philippines. jvgermar@yahoo.com.
Maria Julieta V
MJ
Germar
Facharzt für Frauenheilkunde und Geburtshilfe, Hamburg, Germany. klaus@dr-peters.net.
Klaus
K
Peters
Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville/Department of Microbiology, The Royal Children's Hospital, Parkville/Murdoch Children's Research Institute, Parkville/Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia. suzanne.garland@thewomens.org.au.
Suzanne M
SM
Garland
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Anne
A
Szarewski
Department of Gynaecology, University Hospital KU Leuven Gasthuisberg, Leuven, Belgium. willy.Poppe@uz.kuleuven.ac.be.
Willy A J
WA
Poppe
Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. broman@docromanowski.com.
Barbara
B
Romanowski
Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg, Wuerzburg, Germany. t.schwarz@juliusspital.de.
Tino F
TF
Schwarz
Multidisciplinary Breast Clinic and Gynaecological Oncology, Antwerp University Hospital, University of Antwerp, Antwerpen, Belgium. wiebren.tjalma@uza.be.
Wiebren A A
WA
Tjalma
Unit of Infections and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO), IDIBELL, CIBER-ESP, L'Hospitalet de Llobregat, Avda. Gran via 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. x.bosch@iconcologia.net.|Network on Cooperative Cancer Research, RTICC, Catalonia, Spain. x.bosch@iconcologia.net.
F Xavier
FX
Bosch
4Clinics, Paris, France. mcbozonnat@4clinics.com.
Marie-Cecile
MC
Bozonnat
GlaxoSmithKline Vaccines, Wavre, Belgium. FRANK.STRUYF@GSK.COM.
Frank
F
Struyf
GlaxoSmithKline Vaccines, King of Prussia, PA, USA. Gary.O.Dubin@gsk.com.
Gary
G
Dubin
GlaxoSmithKline Vaccines, Wavre, Belgium. DOMINIQUE.X.ROSILLON@GSK.COM.
Dominique
D
Rosillon
GlaxoSmithKline Vaccines, Wavre, Belgium. LAURENCE.X.BARIL@GSK.COM.
Laurence
L
Baril
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015994:Incidence; D030361:Papillomavirus Infections / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012725:Sexual Behavior / Q000706:statistics & numerical data*; D012747:Sexual Partners; D013030:Spain / Q000453:epidemiology; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology*