Oncology
High-grade anal intraepithelial neoplasia: Progression to invasive cancer is not a certainty

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Abstract

Background

The incidences of high-grade anal intraepithelial neoplasia (HSIL) and superficially invasive squamous cell carcinomas (SISCCA) related to human papillomavirus (HPV) have increased. These lesions can progress to invasive anal cancer. The aim of the study was to assess the clinical outcome with a special focus on the healing rate.

Methods

Forty-six consecutive patients (M/F: 35/11; HIV+: 30) with histologically proven HSIL lesions (N = 41) or SISCCA (N = 5) were enrolled in a follow-up survey.

Results

Of the 46 patients, 40 were treated by excision (n = 9), electrocoagulation (n = 13), topical treatment (n = 2) or combined strategies (n = 16). After a mean follow-up of 35 (27–43) months, only one patient progressed to an invasive cancer. Regression and healing were observed in 14 (30%) and 15 (33%) patients. The cumulative probabilities of healing were 14%, 49% and 74% after 1, 3 and 5 years. None of the current smokers healed. Heterosexual patients, sexual abstinence, patients older than 44 years old, non-smokers, patients without any past history of condyloma and those with less than 2 high-risk HPVs at baseline were more likely to heal.

Conclusion

Progression to invasive cancer is a rare event. Large, prospective cohort studies are needed to plan coherent strategies for both follow-up and treatment.

Introduction

The incidences of anal cancer and its putative precursor (high-grade squamous intraepithelial lesions: HSIL) have greatly increased in recent decades [1], [2], [3] particularly in special population subgroups: men who have sex with men (MSM), those infected with human immunodeficiency virus (HIV), and women with previous cervical human papillomavirus (HPV)-related disease [4].

Anal carcinoma increased from 0.2 to 0.5/100 000 person-years among men and from 0.7 to 1.3/100 000 person-years among women from 1982 to 2012 [3].

Regarding cervical cancer, it is widely recognized that HSIL and superficially invasive squamous cell carcinoma (SISCCA) can preclude invasive cancer. The latter is defined as a nearly stage tumours ≤10 mm, corresponding to HSIL which has an invasive depth of ≤3 mm from the basement membrane of the point of origin, with horizontal spread of ≤7 mm at its maximal extent [5]. Both types of lesions are induced by persistent infections of carcinogenic HPV [6], [7]. Conventionally, they are likely to progress to an invasive cancer [5]. Little is known about the natural history of anal HPV infections and HSIL. One study estimated a HSIL regression rate of 23.5% per year [8].

The lack of data about the natural progression of HSIL and SISCCA to invasive cancers has led to unclear and controversial therapeutic strategies. Management of HSIL varies according to the doctor's expertise, ranging from expectant management with close surveillance [9], [10] to surgical treatment [11], topical application of chemotherapeutic agents [12] or photodynamic therapy [13]. To date, the recommended treatment for SISCCA is radiotherapy, but it has been associated with anatomical and functional side effects unless effective [14], [15], [16]. After we collected the data of consecutive patients with histologically proven HSIL, the aim of this study was to assess the clinical outcome with a special focus on the healing rate.

Section snippets

Patients

This cross-sectional study was conducted in a single tertiary gastroenterology unit (Rennes University Hospital, France) using the records of a central database. All patients with histories of HSIL (only AIN3 in the former classification) or SISCCA proven on anal biopsy, from March 2002 to May 2014, were invited to participate in a new evaluation. Medical records, using both retrospective (2002–2006) and prospective (2007–2014) databases, were extracted with special emphases on MSM and women

Population

From March 2002 to June 2014, 59 patients with HSIL or SISCCA on biopsy were referred to the Rennes University Hospital, France. We excluded 8 patients due to misdiagnoses: they had a true invasive anal squamous carcinoma at the time of initial diagnosis with a discrepancy between histological consideration and macroscopically ulcerative and infiltrative aspects. As a result, 51 patients with histologically confirmed HSIL or SISCCA were available for follow-up. Five patients (9.8%) (4 patients

Discussion

This study, analysing the clinical outcome of anal dysplasia, was the first to define the factors and to quantify the healing of HSIL in a cohort of HIV-infected and uninfected-patients.

The data of the present study emphasize some aspects of the clinical outcome of HSIL.

HSIL is not only an HIV+ related disease. Our data emphasized that a large proportion of HSIL and SISCCA lesions were found in HIV-uninfected, heterosexual, immunocompetent patients (11 patients, 21.5%) (including 4 active

Conclusion

Progression to cancer was a rare event after a three-year follow-up. Clinical regression and healing occurred far more commonly in the clinical outcome of HSIL. This finding suggested that patients might not require treatment in the initial phase of the diagnosis. Tobacco, sexually active lifestyles, homosexual sex, a number of high risk viruses at baseline and a past history of condyloma seemed to be predictive factors for more difficult healing. Future larger-scale studies are necessary to

Conflict of interest

None declared.

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