SquamousIntraepithelialLesion(SIL,CervicalIntraepithelialLesion)
HPV-related carcinogenesis begins with the precancerous epithelial change termed SIL, which usually precedes the development of an overt cancer by many years, sometimes decades. In support of this idea, SIL peaks in incidence at about 30 years of age, whereas invasive carcinoma peaks at about 45 years of age.
The classification of cervical precursor lesions has evolved with time. The current terminology is a two-tiered system that not only reflects the biology of the disease but also patient management, replacing a three-tiered system.
SIL is divided into low-grade squamous intraepithelial lesion (LSIL), still often referred to as cervical intraepithelial neoplasia I (CIN I), and high-grade squamous intraepithelial lesion (HSIL), encompassing cervical intraepithelial neoplasia II and III (CIN II and III) of the previous three-tiered system.
LSIL is associated with productive HPV infection and does not progress directly to invasive carcinoma. Actually, most LSILs regress and only a small percentage progress to HSIL.
HSIL demonstrates increased proliferation, arrested epithelial maturation, and lower levels of viral replication. LSIL is not treated as a premalignant lesion, whereas HSIL is considered at high risk for progression to carcinoma.
Importantly, LSIL is 10 times more common than HSIL and while HSILs are precancerous, the majority of them fail to progress to cancer and may even regress. Patient management rests on the histopathologic diagnosis as discussed later. As shown in
Table 19.1 , the decision to treat HSIL and to observe LSIL is based on differences in the natural histories of these two groups of lesions.
Cervical precancerous lesions are associated with abnormalities in cytologic preparations that can be detected long before any abnormality is visible on gross inspection. Early detection of SIL is the rationale for the Papanicolaou (Pap) test, in which cells are scraped from the transformation zone and examined microscopically. The Pap smear remains the most successful cancer-screening test ever developed. In the United States, Pap screening has dramatically lowered the incidence of invasive cervical tumors to about 13,000 cases annually with a mortality of about 4000 per year; in fact, cervical cancer no longer ranks among the top 10 causes of cancer deaths in U.S. women. Paradoxically, the incidence of SIL has increased to its present level of more than 50,000 cases annually. Increased detection has certainly contributed to this. The U.S. Food and Drug Administration has approved testing for HPV DNA in cervical scrapings. This test is highly sensitive but has lower
Table19.1NaturalHistoryofSquamousIntraepithelialLesions(SILs)
HSIL(CINII,III)30%60%10%(tocarcinoma) aProgressionwithin10years.LSIL,Low-gradeSIL;HSIL,high-gradeSIL.
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Fig.19.6Spectrumofsquamousintraepitheliallesions(SIL)withnormalsquamousepitheliumforcomparison:LSILwithkoilocytoticatypia;HSILwithprogressiveatypiainalllayersoftheepithelium;andHSILwithdiffuseatypiaandlossofmaturation(carcinomainsitu,far right image).