Editing Anal neoplasms (section)

== '''Squamous     intra-epithelial lesions (SIL)''' ==

** Dysplastic changes in the      anal canal that are thought to be precursor lesions to invasive anal      carcinoma
** '''Risk      factors'''
*** HPV 6, 11, 16, 18
**** Especially HPV 16 and 18
**** Small DNA viruses
**** HPV transcription products        directly bind to p53, thus knocking out the tumour suppressor gene
**** There may also be other        impacts
*** Anal warts
*** Multiple sexual partners
*** Anal receptive intercourse
*** History of rectal discharge
*** IVDU
*** Immunosuppression including       HIV and transplant
*** Smoking
*** History of cervical/vulvar       dysplasia or cancer
** '''Histopathology/nomenclature'''
*** Roughly divided into       low-grade SIL (LSIL) and high-grade SIL (HSIL)
**** LSIL is diagnosed when        abnormal basaloid cells extend less than one-third of the thickness of        the epithelium above the basal layer.
**** HSIL shows abnormal        basaloid cells extending into the upper layers of the squamous        epithelium.
*** HSIL is premalignant and       may progress to invasive cancer, whereas LSIL is not a direct precursor       but is considered a risk marker for having HSIL in the future.
**** LSIL seems to regress        within two years in about half of patients, and progress to HSIL in        about 16%, although these numbers are not very precise at all.
**** HSIL can also regress, but        less likely, and can progress to anal cancer in about 2% by 4 years
*** Prior classification was       AIN 1, 2, or 3, depending on the severity of the morphologic changes.       This has been mostly overtaken by SIL in professional literature for       simplicity (there was lots of inter-observer unreliability between AIN 2       and 3) and improved understanding (it is not really a morphologic       continuum, as previously thought). AIN 1 roughly corresponds to LSIL,       and AIN 3 to HSIL. P16-negative AIN 2 is LSIL and p16-positive AIN 2 is       HSIL.
*** Bowen's Disease was       previously used to refer to AIN 3 disease, although I think this is       quite old terminology now
** Presentation
*** Typically asymptomatic
*** Can have pruritis, pain,       burning, bleeding, sometimes a mass
*** Erythematous, scaly skin       change
** Staging
*** Mapping punch biopsies (can       also do this with high-resolution anoscopy, but more commonly done with       patient in lithotomy)
**** Dilute acetic acid is        applied to epithelium of anal canal and perianal region
**** Tissues that harbour AIN        turn acetowhite
**** Lugol's solution can then        be applied - those areas that fail to stain are suspicious for        dysplasia, and should be biopsied - because they are de-differentiated        and don't take up iodine normally
**** Colposcope can be used for        high-resolution anoscopy
*** Excision for histologic       evaluation
** Screening
*** High-risk individuals (HIV       > 35yo, women with HPV-associated genital cancers, solid organ       transplant recipients, other immunocompromised patients
*** Pap smear every 2-3 years
** Prevention
*** Quadrivalent HPV vaccines
** Management
*** Approach:
**** Considerable controversy.        The overall risk of progression is not well-established, so it is        difficult to determine how aggressively to treat it.
**** Topical - imiquimod,        podophyllin, 5-FU, 80% trichloroacetic acid (TCA)
**** Ablative - excision, IRC,        and thermal ablation
*** Intra-anal HSIL: TCA where       available for small lesions, or targeted ablation with IRC, RFA or       electrocautery. Local ablation for larger lesions, although don't treat       >50% of the transition zone at a time. Other topical therapies may       also be used.
*** Perianal HSIL: same as       intra-anal.
*** LSIL: UTD says treatment is       optional.