Atypical Glandular Cells of Undetermined Significance: Outcome Predictions Based on Human Papillomavirus Testing

Abstract

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.

Is Improved Detection of Adenocarcinoma in Situ by Screening a Key to Reducing the Incidence of Cervical Adenocarcinoma?

“…8,12,13,[18][19][20][21] With increasing evidence suggesting the etiolog- ic role of oncogenic human papillomaviruses (HPVs) in cervical AC, 8,22 the recent past has witnessed an influx of reports implicating the utility of HPV testing in the diagnosis of AIS, AC and their precursors. 23,24 This is exactly what happened few years earlier for SCC and its precursors, when Pap smear screening was recommended to be replaced or supplemented by HPV testing; that debate still continues. 8,25 Concerning the reduction of incidence of and mortality from AC, the key question is whether the increased detection of AIS is best achieved by (1) cytologic screening; (2) adjunct diagnostic tools, such as HPV testing; or even (3) immunohistochemistry for molecular markers, such as p16 INK4a .…”

“…8,25 Concerning the reduction of incidence of and mortality from AC, the key question is whether the increased detection of AIS is best achieved by (1) cytologic screening; (2) adjunct diagnostic tools, such as HPV testing; or even (3) immunohistochemistry for molecular markers, such as p16 INK4a . [5][6][7]23,24,26 Elucidating this issue has important implications for future screening strategies, which are likely to be different in low and high resource settings. 1,2,4,8,25 An important step forward in validating the concept of AIS as a predominantly screening-detected disease is made in a paper by Mitchell et al, published in this issue of Acta Cytologica.…”

Stellenwert des Nachweises von humanem Papillomvirus in der Früherkennung des Zervixkarzinoms

“…Bei AGC «not otherwise specified» (AGC-NOS) ist das Risiko einer höhergradigen Läsion jedoch geringer, so dass kolposkopische Kontrollen im Abstand von 4-6 Monaten empfohlen werden [35]. Neue Studien haben jedoch gezeigt, dass bei zytologisch glandulären Läsionen der HPV-Test einen hohen Voraussagewert für behandlungsbedürftige Läsionen von etwa 60% hat [41]. Dementsprechend scheint es uns vertretbar, bei onkogenen HPV-positiven AGC-NOS die Konisaton mit endozervikaler Kürettage zu indizieren.…”

Guideline zum Vorgehen bei suspektem und positivem zytologischen Abstrich der Cervix uteri (überarbeitete Fassung, Version 2.4)

“…Die kumulative Inzidenz eines invasiven Zervixkarzinoms nach Konisation wegen CIN III liegt nach 10 Jahren bei 1% [10]. Der negative Voraussagewert des HPV-Tests nach CIN-Therapie wird zwischen 92 und 100% angegeben, was auch für Frauen mit befallenen Resektionsrändern gilt [9,10,22,48,50,59,67,86,141]. Der positive Voraussagewert des HPV-Tests 6 Monate nach Konisation ist höher als in der Screeningsituation und beträgt 24% [141].…”