The risk of cervical cancer in relation to hormonal contraceptives in women that are HPV-DNA carriers. Pooled analysis of the IARC multicentric case-control study

The risk of cervical cancer in relation to hormonal contraceptives in women that are HPV-DNA carriers. Pooled analysis of the IARC multicentric case-control study

Victor Moreno, Servei d' Epidemiologia i Registre del Cncer, Institut Catal d' Oncologia, Barcelona, Spain
F. Xavier Bosch, Servei d' Epidemiologia i Registre del Cncer, Institut Catal dÕ Oncologia, Barcelona, Spain
Nubia Muoz, International Agency for Research on Cancer, Lyon, France
Silvia Franceschi, Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano, Italy
Saibua Chichareon, Assoc. Prof., D. of Obstetrics and Gynecology, F. of Medicine, PSU.
Cora Ngelangel, Clinical Epidemiology Unit, Philippine General Hospital. Manila, The Philippines
Eduardo Caceres, Centro de Investigacin del Cncer, Inst. Nacional de Enfermeades Neoplsicas, Lima, Peru
Joseph Eluf-Neto, Depto. Medicina Preventiva, Faculdade Medicina, University Sao Paulo, Brazil
Brahim EL Gueddari, Institut Nacional dÕOncologie, Rabat, Morocco
Jan M.M. Walboomers, Free U. Hospital, Amsterdam, The Natherlands
Corresponding e-mail : csaibua@ratree.psu.ac.th

Grant : International Agency for Research on Cancer
Presented : The 18th International Papillomavirus Conference, 23rd - 28th July 2000, Barcelona, Spain
Key words : hormonal contraception, HPV-DNA carriers

Introduction : A substantial number of studies have suggested that hormonal contraceptives (HC) may be related to cervical cancer (CC). However, most did not consider HPV, the central cause of cervical cancer. Thus, an important proportion of control women who were not carriers of HPV may not be susceptible of developing CC irrespective of their hormonal exposures. We present a combined analysis of case control studies restricted to HPV-DNA positive women.

Methods : Between 1985 and 1998 the IARC conducted 8 case-controls studies in Thailand, Philippines, Morocco, Brazil, Peru, Paraguay, Colombia and Spain. CC cases (N = 1882) were his-tologicaly confirmed. Controls (N = 1968) were hospital lased frequency-matched by age except in Spain and Colombia that were population based. In Colombia and Spain 2 additional studies on CIN3 cases (N=512) were also performed in family planning clinics. Controls (N=456) were recruited in the same clinics matched by age and date of diagnosis. All were personally interviewed about HC use, duration of use, start and age stop. Estimation of risks have been derived from logistic-regression models adjusted for study, age, education, sexual partners, pregnancies, age at first sexual intercourse and screening history.

Results : A total of 1768 cases and 262 controls were positive for HPV-DNA, corresponding to 73.9% of the cases and 10.8% of the controls of the original studies. Ever HC use was associated with a significant increase in risk of CC (OR = 1.47[1.02-2.12]). Use of HC for < 5 years was not related to CC (OR = 0.77[0.46-1.29]). Risk increased for 5-9 years of use (OR = 2.72[1.36-5.46]) and for 10+ years (OR = 4.48[2.24-9.36]). Risk was significantly increased for recent use : for < = 5 years after cessation OR = 3.33[1.91-5.81]. After 6+ years since cessation the risk estimate was reduced to OR = 0.93(0.61-1.41). However, this decrease only occurred for women exposed during short duration (<=5 yr). Findings were homogeneous among studies and did not vary importantly between CIN III and invasive cases.

Conclusions : Long term use of HC is a cofactor that increases up to 4-fold the risk of CC among women that are carriers of HPV-DNA. No appreciable HC-related increase in risk was found among women who were negative for HPV-DNA.

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