Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

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As the incidence of anal cancer increases, researchers are looking to identify the cause of this trend and determine the gold standard of treatment.

Much of the increase in anal cancer incidence is associated with an increase in populations that are at-risk, including people with human immunodeficiency virus (HIV)–positive, men who have sex with men (MSM), organ transplant recipients, and women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN).

Within this paper, researchers focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN). Risk factors for HPV and SCC are commonly the particular behaviors that predispose individuals to HPV infection or immunosuppression. Because the symptoms of AIN are similar to symptoms associated with common benign anorectal diseases, all patients should be properly assessed to avoid delays in diagnosis. However, there currently are no guidelines in the U.K. for the routine screening for anal cancer.

After a patient is diagnosed, the recommended treatment for all four stages of anal SCC, except for small T1 tumors of the anal margin, is concurrent chemotherapy and radiotherapy. This treatment is recommended over radiotherapy alone. Otherwise, a patient can undergo radical surgery to improve local control.

The diagnosis and management of anal cancer is challenging to the modern physician and surgeon, this is due to the common reluctance of patients to see their doctor regarding anorectal problems and because symptoms of anal neoplasia are often similar to common benign anorectal diseases.

Health care professionals continue to debate about screening in high-risk groups and a country-wide HPV vaccination program, but further discussion is needed, particularly if the number of patients with AIN continues to increase.

Human papilloma virus is a risk factor for anal intraepithelial neoplasia.
Human papilloma virus is a risk factor for anal intraepithelial neoplasia.

Abstract

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer.

This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus.

Keywords: anal cancer, squamous cell carcinoma, basaloid carcinoma, surgery

Introduction

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000.1,2 Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM) are at increased risk of anal cancer.

Organ transplant recipients and women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are also known to have a greater risk for anal cancer.3–5This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management and preventing its development into squamous cell carcinoma (SCC) of the anus.

Etiology

The most important risk factors for HPV and SCC are behaviors that predispose individuals to HPV infection or immunosuppression. Epidemiological studies have shown that approximately 85% of anal cancers are associated with HPV infection, predominately HPV types 16 (HPV-16) and 18 (HPV-18).

HPV-16 and -18 are common in Europe, but in South America and other parts of the world, other HPV sub-types may be more prevalent. AIN, the potential precursor lesion of anal cancer, is common among HIV-positive men who have sexual intercourse with men and is considered analogous to CIN.

Recent literature has demonstrated a significant increase in AIN, but the actual overall incidence in the general population is unknown. AIN may be subdivided into low-grade AIN (LGAIN) and high-grade AIN (HGAIN). LGAIN reflects active HPV replication, is not considered precancerous, and includes condyloma and AIN 1. HGAIN comprises AIN 2 and AIN 3; AIN 3 is considered precancerous.4

Two recent papers reported HPV prevalence of AIN 1 (91.5%) and AIN 2/3 (93.9%), respectively, among 671 (AIN 1) and 609 (AIN 2/3) patients with AIN.3,6Anal intercourse is among the presumed mechanisms by which HPV is introduced into the anal canal. Men with HIV are also at increased risk for anal cancer.7,8

Studies have shown that HPV infection of the anal region in both heterosexual men and non–HIV-infected men is also becoming common. Studies have shown that the prevalence of HPV DNA, detected in 222 heterosexual men, was 16.6% for the anal canal and 21.3% for the perianal area. Of the patients with anal HPV infection, fully 33.3% had an oncogenic high-risk HR-HPV type.9,10

In comparing only HIV-negative men (1305 heterosexual versus 176 homosexual), they found anal canal HPV prevalence of 12.2% and 47.2% in these groups, respectively. Two previous studies examining heterosexual men have reported anal HPV DNA prevalence of 8% and 35%, respectively.11,12

With regards to HIV-negative women, anal HPV infection data three studies have reported a prevalence of 27% anal HPV infection and after average follow-up period of 1.3 years, 70% of women developed incident anal HPV infection and abnormal cytology of 66.7% and 42%, respectively, HPV infection having been detected via anal cytology.13,14 

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