A multinational case-control study on the risk of cervical cancer linked to 25 HPV, Types : Which are the high-risk types?

A multinational case-control study on the risk of cervical cancer linked to 25 HPV, Types : Which are the high-risk types?

Nubia Muoz, International Agency for Research on Cancer, Lyon, France
F. Xavier Bosch, Institut Catal dÕ Oncologia, Barcelona, Spain
Saibua Chichareon, Assoc. Prof., D. of Obstetrics and Gynecology, F. of Medicine, PSU.
Jos Eluf-Neto, U. of So Paulo, Brazil
Cora Ngelangel, Philippine General Hospital, Manila, The Philippines
Caceres, E., Mes-Heller Cancer Center, Lima, Peru
Roln, P.A., D. Pathology, Ministry of Health, Asuncin, Paraguay
Bayo, S., National Inst. of Public Health Research, Ministry of Health, Bamako, Mali
Chaouki, N., National Cancer Inst., Rabat, Morocco
Shah, K.V., Johns Hopkins U., Baltimore, MD. USA.
Jan M.M. Walboomers, Free U. Hospital, Amsterdam, the Netherlands
Chris J.L.M. Meijer, Free U. Hospital, Amsterdam, the Netherlands
Corresponding e-mail : csaibua@ratree.psu.ac.th

Grant : International Agency for Research on Cancer
Published : The 18th International Papillomavirus Conference, 23rd-28th July 2000, Barcelona, Spain
Key words : cervical cancer, HPV types

Background : In 1995, the International Agency for Research on Cancer (IARC) evaluated all relevant data on the carcinogenicity of HPV and concluded that there was sufficient evidence to categorize HPV types 16 and 18 as human carcinogens, but that the existing evidence was limited or inadequate for the other HPV types (IARC Monograph No 64, 1995). Since the IARC evaluation, we have completed case-control studies on cervical cancer in various populations that will allow updating these conclusions.

Methods : From 1985 to 1997 a total of 2,288 consecutive women with a histological diag- nosis of cervical squamous cell carcinoma were recruited from the main hospitals of Cali, Colombia (441); 9 provinces in Spain (469); So Paulo, Brazil (176); Asuncin, Paraguay (109); Lima, Peru (173); Bamako, Mali (79); Rabat, Morocco (152); Hat Yai, Thailand (345); and Manila, the Philip- pines (344). In Colombia and Spain the studies were population-based and in 7 other countries they were hospital-based. A total of 2,513 age-matched control women were recruited from the same hospitals as the cases in the hospital-based studies and were randomly selected from the general population in Spain and Colombia. All study women were interviewed using a standardized ques-tionnaire and were then submitted to a pelvic examination and collection of cervical scrapes for PAP smears and for HPV DNA detection. A tumour biopsy was also collected from cases. 84% of the case women and 85% of the control women provided cervical specimens for HPV DNA detec- tion. HPV DNA detection was carried out at a central laboratory using PCR-based assays. 3% of the case specimens and 8% of those from controls were (-globin negative).

Results : HPV DNA prevalence was 91% in cases, ranging form 75% in Colombia to 98% in Paraguay and among controls it was 13.7%, ranging from 5.4% in Spain to 21.6% in Morocco. The age and center-adjusted OR was 83.3 (95% CI : 54.9-105.3). The 4 most common HPV types and their Ors among 1,545 cases with single infections were : HPV 16 : 59%, OR = 182; HPV 18 : 12%, OR = 231; HPV 45 : 4.8%, OR = 148; HPV 31 : 3.7%; OR = 71.5. Other less common HPV types showing equally high Ors were : HPV 33 : OR = 77.6; HPV 35 : OR = 34.8; HPV 51 : OR = 42.7; HPV 52 : OR = 145.7; HPV 58 : OR = 78.9; HPV 59 : OR = 347.3 Multiple HPV types were detected in 7.3% of the cases and 1.9% of the controls, and did not show a significantly increased risk (OR = 54.5; 95% CI : 35.5-83.6) over women positive for only one HPV type (OR = 86.6; 95% CI : 68.2-110). 97 (72%) out of 134 cases with multiple HPV types included HPV 16 or 18. Among controls 11 (30%) of multiple types included HPV 16 or 18. The most common types among cases were also the most common types among control women : HPV 16 : 30.3%; HPV 18 : 8.2%; HPV 31 : 4.8%; and HPV 45 : 3.9%.

Conclusions : Squamous cell carcinoma of the cervix is strongly associated with HPV in 9 countries around the world. The association is equally strong for the most common HPV types, HPV 16 and 18 as well as for the less common types : HPV 45, 31, 33, 35, 51, 52, 58 and 59. These find- ings indicate that in addition to HPV 16 and 18, HPVs 31, 33, 35, 45, 51, 52, 58 and 59 can now be considered as carcinogenic.

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