Investigating the significance of smoking in cervical cancer

Posted on: 01 October 2020

Human papillomavirus (HPV) is considered the strongest risk factor for cervical cancer. Although, HPV is a very common infection, not all infections will lead to a cancer diagnosis. Other co-factors may be involved in the development of this particular type of cancer.

Dr Christine White and her team, led by Professor John O’Leary at Trinity St James’s Cancer Institute (TSJCI) have investigated smoking as a co-factor for high-grade cervical disease in women who were positive for HPV.

The researchers investigated:

1) are women who smoke more likely to have an active HPV infection and

2) are women with active infections who smoke at a higher risk of having a high-grade cervical lesion diagnosed?

The study was performed on women attending a colposcopy clinic at the National Maternity Hospital, Dublin. In order to accurately determine how much tobacco, smoke a woman was exposed to the team performed a nicotine test on a urine sample. To determine if a HPV infection was active they used a biomarker test called p16/Ki-67.

The findings showed that women who were HPV positive and who smoked were more likely to have to positive p16/Ki-67 result compared to HPV positive women who did not smoke. Furthermore, in women who were p16/Ki-67 positive the risk of having high-grade cervical disease was doubled in smokers compared to non-smokers.

The exact way in which smoking causes this increased risk is unknown, however it is known that smoking reduces the number of immune cells in the cervix which could potentially facilitate an active HPV infection.

Why is this study important?

These findings suggest that smoking not only increases the risk of having an active infection but also increases the risk of a subsequent high-grade disease diagnosis.

The study is important because while the role of smoking and risk of high-grade pre-cancer has been established internationally, the role of smoking and risk of HPV infection is less clear. Many studies are based on self-reported smoking behaviours. However, it is well recognised that patients under report smoking habits, thus analyses may be affected by misclassification which could lead to an underestimation of the true association of smoking and cervical cancer.

This study provides a unique analysis on the risk of exposure to tobacco smoke and active HPV infection, which has not been shown before. The team’s findings, based on longitudinal data, have revealed for the first time that women with elevated urine concentrations of nicotine, indicative of exposure to tobacco smoke, are at a higher risk of p16/Ki-67 co-expression, a marker of an active HPV infection.

The findings generated important data that has shown that the risk of high-grade cervical disease is doubled in HPV positive women who smoke compared to those who don’t smoke. This study identified that there is a higher proportion of smokers attending colposcopy clinics compared to the general public. The number of women reporting as smokers represented 41.5% of the study population. This represents a high proportion compared to the overall Irish population where the prevalence of female smokers was only 22% at the time of the study (2010-2013).

This not only endorses the fact women who smoke are at an increased risk of cervical lesions but potentially promotes colposcopy clinics as a setting for introducing smoking cessation campaigns. Health scares and minor illness often trigger short-term consideration to quitting smoking in women. This highlights the need to continuously reinforce the importance of quitting smoking to women at both colposcopy visits and follow up smear clinics.

Dr Christine White, Department of Histopathology and Morbid Anatomy, Trinity College said:

 Research and research funding are fundamental to driving health policy and improving healthcare practice. Through research we can increase our knowledge and understanding of cancer and apply evidence-based practices to reduce the burden of cancer by improving prevention, detection and treatment of cancer. By increasing our understanding of what drives certain cancers we can also educate the public on impact of cancer risk factors such as smoking and HPV.

Trinity St James’s Cancer Institute (TSJCI)

The mission of Trinity St James’s Cancer Institute is to integrate innovative and ground-breaking cancer science with compassionate, multi-disciplinary , patient-focussed care through translation of key research findings into incremental advances in the prevention, diagnosis and treatment of cancer.

Further information on this research:

Exposure to tobacco smoke measured by urinary nicotine metabolites increases risk of p16/Ki-67 co-expression and high-grade cervical neoplasia in HPV positive women: A two -year prospective study, can be viewed here:


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