specificity than the Pap smear, and specific guidelines for its use have not been well established. One consideration is that while most women acquire HPV infections in their early 20s, these are usually cleared by the immune system and never progress to SIL, a process that occurs over many years. For this reason, HPV DNA screening is only recommended for women aged 30 or older, as a positive test at this age is more likely to identify an individual with a persistent infection that may lead to cervical neoplasia.
The quadrivalent HPV vaccine for types 6, 11, 16, and 18, and the more recently introduced 9-valent vaccine, are very effective in preventing HPV infections and are expected to greatly lower the frequency of genital warts and cervical cancers associated with these HPV genotypes. Despite its efficacy, vaccination does not supplant the need for routine cervical cancer screening—many at-risk women are already infected, and current vaccines protect against only some of the many oncogenic HPV genotypes.
Fig.19.6 illustratesthethreestagesofSIL.LSILischaracterizedbydysplasticchangesinthelowerthirdofthesquamousepitheliumandkoilocytoticchangeinthesuperficiallayersoftheepithelium.InHSIL(CINII),dysplasiaextendstothemiddlethirdoftheepitheliumintheformofvariationincellandnuclearsize,heterogeneityofnuclearchromatin,andthepresenceofmitoses,someatypical,abovethebasallayerextendingintothemiddlethirdoftheepithelium.ThesuperficiallayerofcellsinCINIIstillshowsdifferentiationandoccasionalkoilocytoticchangesHSIL(CINIII)ismarkedbyalmostcompletelossofdifferentiation,evengreatervariationincellandnuclearsize,chromatinheterogeneity,disorderlyorientationofthecells,andabnormalmitoses,changesthataffectvirtuallyalllayersoftheepithelium.Koilocytoticchangeusuallyisabsent.Thesehistologicfeaturescorrelatewiththecytologicappearancesshownin
Fig.19.7
Fig.19.7Cytologicfeaturesofsquamousintraepitheliallesion(SIL)inaPapanicolaousmear.Superficialsquamouscellsmaystaineitherredorblue.
(A)Normalexfoliatedsuperficialsquamousepithelialcells.(B)Low-gradesquamousintraepitheliallesion(LSIL).(CandD)Bothhigh-gradesquamousintraepitheliallesions(HSILs).Notethereductionincytoplasmandtheincreaseinthenucleus-to-cytoplasmratioasthegradeofthelesionincreases.Thisobservationreflectstheprogressivelossofcellulardifferentiationonthesurfaceofthecervicallesionsfromwhichthesecellsareexfoliated(see
Fig.19.6).
(Courtesy of Dr. Edmund S. Cibas, Brigham and Women’s Hospital, Boston, Massachusetts.) http://ebooksmedicine.net
SIL is asymptomatic and comes to clinical attention through an abnormal Pap smear result. These cases are followed up by colposcopy, in which acetic acid is used to highlight the lesions so they can be biopsied. Women with biopsy-documented LSIL are managed conservatively with careful observation, whereas HSILs and persistent LSIL are treated with surgical excision (cone biopsy). Follow-up smears and clinical examination are required in patients with HSIL, as these women remain at risk for HPV-associated cervical, vulvar, and vaginal cancers.