Obstacles to the Early Detection of Endocervical Adenocarcinoma

Abstract

We observed that the ratio of in situ to invasive carcinomas of the cervix is significantly greater for squamous than for glandular lesions. We wondered whether Pap smears were less effective for the identification of in situ glandular lesions. The purpose of this study was to determine if the location, extent of disease, and growth patterns of endocervical adenocarcinomas influence the ability to detect malignant cells by Pap smears. Medical records, doctor's office records, and all pathology materials (reports and slides) including Pap smears, biopsies, LEEP/cone biopsies, and hysterectomy specimens from 53 consecutive patients diagnosed with endocervical adenocarcinomas were examined at New York University Medical Center (a total of 654 pathology slides and 51 Pap smears were reviewed). Findings were correlated for each patient using gross descriptions and histopathology and stratified by location/extent of disease and growth pattern (exophytic or endophytic or both). Ten patients had in situ disease, seven (70%) of which involved the transformation zone (TZ); all seven of these were identified by Pap smears. In contrast, of the other three cases that did not involve the TZ but were confined to the endocervix, only one was identified by Pap smear. Forty-three patients had invasive disease. Twenty involved the TZ, and 23 involved the endocervix but spared the TZ. Of the 20 tumors involving the TZ, 11 (55%) were identified by Pap smears, whereas of the 23 sparing the TZ, 11 (47.8%) were diagnosed by Pap smear. Among the 23 patients with invasive disease that spared the TZ, 6 (26%) had a documented history of negative Pap smears at New York University within 3 years of diagnosis. Conversely only 1 of the 20 patients with TZ involvement had a history of negative Pap smears, and 3 patients in this group denied having had Pap smears for several years. Including all 53 patients, a significantly higher proportion were not detectable by Pap smear if the TZ was spared (54% versus 25%, p = 0.036). Of the 23 invasive cancers that spared the TZ, 6 (14%) had verified negative Pap smears. These lesions did not shed malignant cells onto Pap smears. Noteworthy was the finding that two of these six lesions extended from the endocervix upward, through the stroma, and into the endomyometrium of the lower uterine segment. Four extended downward into the exocervix through the stroma, sparing the surface mucosa; one reached the upper vagina. All six displayed an endophytic growth pattern.

Pap smear screening history of women with squamous cell carcinoma and adenocarcinoma of the cervix

“…However, it has been shown that a significant number of cervical AC arise above the level of the transformation zone or growing beneath the surface sparing the surface mucosa. 15 These ACs may display an endophytic growth pattern, thus escaping cervical cytology.…”

Significant decrease of adenocarcinoma in situ not reflected in cervical adenocarcinoma incidence in the Netherlands 1989–2003

“…This contrasts with the decrease in squamous cell carcinoma (SCC) since the introduction of screening programmes (Bergstrom et al, 1999;Ronco et al, 2005;Kyndi et al, 2006). Studies have shown that Pap smears are less sensitive in detecting precursor lesions of AC than those of SCC (Etherington and Luesley, 2001;Schoolland et al, 2002;Kalir et al, 2005). This makes the incidence of AC less likely to be influenced by screening (Nieminen et al, 1995;Bergstrom et al, 1999).…”

Adjunctive high-risk human papillomavirus DNA testing is a useful option for disease risk assessment in patients with negative Papanicolaou tests without an endocervical/transformation zone sample

“…30 Fortunately, these tumors appear to be uncommon. Data from the current study indicate that hrHPV DNA testing accurately reflects the increased cross-sectional risk of LSIL and HSIL in women whose Pap tests lack an EC/TZS.…”