Genital warts a marker for increased risk of anogenital cancers, cancers of the head and neck as well as some other malignancies

Infection with genital warts is associated with an increased risk of ano-genital cancers, malignancies of the head and neck and cancers in some other sites, according to the results of a large Danish study published in the online edition of the Journal of Infectious Diseases.

Many of these cancers were associated with high-risk strains of human papilloma virus (HPV), and the risk of these cancers remained elevated up to ten years after diagnosis with genital warts.

“Our findings indicate that patients with genital warts belong to a high risk group in regard to subsequent HPV related cancer,” write the authors. They believe their findings have implications for HPV surveillance and vaccination programmes.

Genital warts are a common sexually transmitted infection affecting millions of patients worldwide. They are caused by HPV, most often HPV-6 and HPV-11, neither of which cause cell changes that can lead to cancer.  However, it is common for patients to be infected with multiple strains of HPV, including those which have been associated with an increased risk of cancer.

Previous studies examining the association between genital warts and the risk of cancer have produced conflicting results. To establish a clearer understanding of this issue, investigators from Denmark examined the medical records of almost 50,000 patients diagnosed with genital warts between 1978 and 2008. They calculated the incidence of anogenital cancers in these patients as well as cancers of the head and neck and malignancies in other sites. These incidences were compared to those observed in the general Danish population cancer registry.

Over 16,000 men and 33,000 women were diagnosed with genital warts in the 30 years of the study. The men were followed for a mean of twelve years after diagnosis, the women for a mean of 13 years.

The total number of cancers observed during the study was 2362. This compared to an estimated 1807 cancers in the general population. Overall, patients with genital warts were 30% more likely to develop a cancer compared to individuals without this malignancy

This elevated risk was mainly attributable to an increased incidence of cancers at HPV-related sites. This risk was higher for men (SIR = 7.2; 95% CI, 5.5-9.2) than women (Standardised Incidence Ratio [SIR] = 2.8; 95% CI, 2.4-3.1).

A total of 29 cases of anal cancer were diagnosed in men diagnosed with genital warts (SIR = 21.5; 95% CI, 14.4-30.9). Men diagnosed with genital warts also had an increased risk of penile cancer (SIR = 8.2; 95% CI, 4.1-14.6).

For women, diagnosis with genital warts was associated with a substantial increase in the risk of cancer of the vulva (SIR = 14.8; 95% CI, 11.7-18.6), followed by anal cancer (SIR = 7.8; 95% CI, 5.4-11.0), vaginal cancer (SIR = 5.9; 95% CI, 2.2-12.9) and cervical cancer (SIR = 1.5; 95% CI, 1.3-1.8).

For both sexes, genital warts were associated with an increased risk of cancers of the head and neck, especially cancer of the tonsils (men, SIR = 4.6; 95% CI, 2.7-72; women, SIR = 4.7; 95% CI, 2.3-8.4). An increased risk of cancers of the mouth, pharynx and larynx was also observed in both sexes.

A diagnosis with genital warts was also associated with the development of cancers at body sites not normally associated with HPV-related cancers.

This included non-melanoma skin cancer, as well as lung, liver and bladder cancer and Hodgkin and non-Hodgkin lymphoma.

The increased risk of many cancers persisted for over ten years after diagnosis with genital warts.

The risk of developing cancer of the anus or vulva was greatest in the first year after diagnosis with genital warts and then fell gradually. However, ten years after diagnosis, the risk of most HPV-related cancers was still moderately increased (SIR = 3.8; 95% CI, 0.8-11.0).

“We found significantly increased rates of anogenital and certain head and neck cancers in individuals diagnosed with genital warts,” write the authors. “For most HPV-related cancers, a sustained excess risk was evident even 10 years after the genital warts diagnosis.”

The investigators offer several possible explanations for the association between genital warts and an increase in the risk of cancer. These include:

• Infection with high-risk strains of HPV.

• Immunological deficiencies.

• Life-style factors such as multiple sexual partners and smoking.

• Localised immune suppression and inflammation.

They believe that further research is needed into the association between genital warts and the risk of skin cancers.

“The results add to the evidence of a link between HPV and ano-genital cancer, head and neck cancer and possibly non-melanoma skin cancer,” conclude the authors. “This study is important to clinicians in relation to the identification of cancers at an early stage…in addition, the results may direct future studies of HPV DNA detection toward different types of tumour and be valuable when estimating health benefits of HPV vaccination.