Risk factors for cervical cancer development
Author: Gunnell, Anthony S
Date: 2007-12-14
Location: Hörsal Atrium, Nobels väg 12B
Time: 09.15
Department: Institutionen för medicinsk epidemiologi och biostatistik / Department of Medical Epidemiology and Biostatistics
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Thesis (605.3Kb)
Abstract
Cervical cancer remains one of the leading causes of cancer mortality
globally, predominantly in less developed countries. It is widely
accepted that certain oncogenic types of HPV (Human papillomavirus) are
necessary causes of cervical cancer development and a number of
co-factors (including smoking) have also been implicated. The
introduction of Papanicolaou testing has achieved a large reduction in
cervical cancer incidence over the last 4 decades however its use is not
without problems, particularly with regards to its relatively low
specificity. Recently HPV vaccines targeting HPV-16 and HPV-18 have been
developed, which hold the promise of reducing cervical cancer incidence
further. In the four studies included in this thesis, we investigate
several risk factors related to cervical cancer formation, test the
efficiency of Pap smear screening in reducing the incidence of the two
main cervical cancer types (cervical squamous cell carcinoma and
adenocarcinoma), investigate possible maternal transmission of cervical
cancer in situ, and estimate the effects that vaccines against HPV-16/18
might have had on the Swedish population over the last 30 years had they
been implemented.
Using a population-based case-control study, we examined the individual risks for cervical cancer in situ (CIS) associated with HPV-16 presence, HPV-16 load, and smoking. After analysis of first cervical smears for 375 case and 363 control women, we found higher increased risks associated with HPV-16 presence in smokers (adjusted OR=14.4; 95% CI 5.6-36.8) than non-smokers (adjusted OR=5.6; 95% CI 2.7-11.2), compared with HPV-16 negative women. Risk for CIS was even higher in smokers with high HPV-16 load (adjusted OR=27.0; 95% CI 6.5-114.2) compared to smokers who were HPV-16 negative. In contrast, non-smokers with high HPV-16 load had a lower risk (adjusted OR=5.9; 95% CI 2.4-14.6). Neither HPV-16 presence nor load were found to significantly interact with smoking status, although significant interaction was found between current smoking status (at first smear) and duration of smoking (p=0.03).
Analysis of Swedish nation-wide data covering 1968-2002 provided evidence for the beneficial nature of Pap smear screening in reducing cervical squamous cell carcinoma (SCC), but not cervical adenocarcinoma (AC). We also found that higher reported CIS incidence rates in certain counties did not lead to future reductions in SCC incidence. This was also the case for adenocarcinoma in situ (AIS) reported, and future AC incidence. On the whole, our results suggest there is over-treatment of CIS. Also it appears likely that inefficiencies exist in the use of Pap smear screening for AC prevention.
In a cohort of mother-daughter pairs, we found a 24% excess risk for CIS in daughters whose mothers exhibited CIS within 10 years after their daughter s conception compared to daughters whose mothers had CIS more than 10 years after their conception. This may conceivably be the result of maternal transmission of HPV during pregnancy or childhood.
Using a population-based cohort of Swedish women, we estimated that a 61.2% reduction in SCC incidence could have been achieved through the removal of HPV-16/18 from the population during 1969-2002. In comparison, removal of all measured high risk HPV types may have reduced SCC incidence by 83.9%. Removal or reduction of HPV-16 and -18 from the Swedish population will give considerable benefit in reducing cervical cancer. However, the risks associated with other non- HPV-16/18 oncogenic types are worthy of consideration in future monitoring and prevention strategies.
Using a population-based case-control study, we examined the individual risks for cervical cancer in situ (CIS) associated with HPV-16 presence, HPV-16 load, and smoking. After analysis of first cervical smears for 375 case and 363 control women, we found higher increased risks associated with HPV-16 presence in smokers (adjusted OR=14.4; 95% CI 5.6-36.8) than non-smokers (adjusted OR=5.6; 95% CI 2.7-11.2), compared with HPV-16 negative women. Risk for CIS was even higher in smokers with high HPV-16 load (adjusted OR=27.0; 95% CI 6.5-114.2) compared to smokers who were HPV-16 negative. In contrast, non-smokers with high HPV-16 load had a lower risk (adjusted OR=5.9; 95% CI 2.4-14.6). Neither HPV-16 presence nor load were found to significantly interact with smoking status, although significant interaction was found between current smoking status (at first smear) and duration of smoking (p=0.03).
Analysis of Swedish nation-wide data covering 1968-2002 provided evidence for the beneficial nature of Pap smear screening in reducing cervical squamous cell carcinoma (SCC), but not cervical adenocarcinoma (AC). We also found that higher reported CIS incidence rates in certain counties did not lead to future reductions in SCC incidence. This was also the case for adenocarcinoma in situ (AIS) reported, and future AC incidence. On the whole, our results suggest there is over-treatment of CIS. Also it appears likely that inefficiencies exist in the use of Pap smear screening for AC prevention.
In a cohort of mother-daughter pairs, we found a 24% excess risk for CIS in daughters whose mothers exhibited CIS within 10 years after their daughter s conception compared to daughters whose mothers had CIS more than 10 years after their conception. This may conceivably be the result of maternal transmission of HPV during pregnancy or childhood.
Using a population-based cohort of Swedish women, we estimated that a 61.2% reduction in SCC incidence could have been achieved through the removal of HPV-16/18 from the population during 1969-2002. In comparison, removal of all measured high risk HPV types may have reduced SCC incidence by 83.9%. Removal or reduction of HPV-16 and -18 from the Swedish population will give considerable benefit in reducing cervical cancer. However, the risks associated with other non- HPV-16/18 oncogenic types are worthy of consideration in future monitoring and prevention strategies.
List of papers:
I. Gunnell AS, Tran TN, Torrång A, Dickman PW, Sparén P, Palmgren J, Ylitalo N (2006). "Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development." Cancer Epidemiol Biomarkers Prev 15(11): 2141-7.
Pubmed
View record in Web of Science®
II. Gunnell AS, Ylitalo N, Sandin S, Sparén P, Adami H-O, Ripatti S (2007). "A longitudinal Swedish study on screening for squamous cell carcinoma and adenocarcinoma; Evidence of effectiveness and over-treatment." Cancer Epidemiology Biomarkers and Prevention. [Accepted]
Pubmed
View record in Web of Science®
III. Gunnell AS, Ripatti S, Sandin S, Sparén P, Ylitalo N (2007). "Cervical cancer in situ in mothers and subsequent risk for daughters: maternal transmission of HPV?" [Submitted]
IV. Gunnell AS, Sparén P, Ripatti S, Adami H-O, Dillner J, Ylitalo N (2007). "Risk for severe dysplasia/cancer in-situ and invasive squamous cell carcinoma conferred by common oncogenic HPV types in Sweden." [Submitted]
I. Gunnell AS, Tran TN, Torrång A, Dickman PW, Sparén P, Palmgren J, Ylitalo N (2006). "Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development." Cancer Epidemiol Biomarkers Prev 15(11): 2141-7.
Pubmed
View record in Web of Science®
II. Gunnell AS, Ylitalo N, Sandin S, Sparén P, Adami H-O, Ripatti S (2007). "A longitudinal Swedish study on screening for squamous cell carcinoma and adenocarcinoma; Evidence of effectiveness and over-treatment." Cancer Epidemiology Biomarkers and Prevention. [Accepted]
Pubmed
View record in Web of Science®
III. Gunnell AS, Ripatti S, Sandin S, Sparén P, Ylitalo N (2007). "Cervical cancer in situ in mothers and subsequent risk for daughters: maternal transmission of HPV?" [Submitted]
IV. Gunnell AS, Sparén P, Ripatti S, Adami H-O, Dillner J, Ylitalo N (2007). "Risk for severe dysplasia/cancer in-situ and invasive squamous cell carcinoma conferred by common oncogenic HPV types in Sweden." [Submitted]
Issue date: 2007-11-23
Rights:
Publication year: 2007
ISBN: 978-91-7357-437-2
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