Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study

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Abstract

Objectives

To determine how human papillomavirus (HPV) positivity of atypical glandular cells (AGCs) affects the predictive values for the presence of high-grade cervical lesions.

Design

Population-based cohort study.

Setting

Stockholm-Gotland region, Sweden.

Participants

Between 17 February 2014 and 30 June 2016, there were 562 women with AGC detected in a cervical sample. Registry linkages up to 30 June 2016 identified 392 women with an associated HPV test and a histopathological follow-up.

Main outcome measure

Presence of a high-grade cervical lesion in the cervical biopsy taken after the AGC smear, in relation to the HPV status of the AGC-containing index smear.

Results

The proportion of HPV-positive AGC was 56% (n=222). In this group, there were six cases of invasive cervical adenocarcinoma, 33 cases of cervical adenocarcinoma in situ and 93 cases of high-grade squamous intraepithelial lesion (HSIL), giving a positive predictive value (PPV) for a cervical high-grade lesion of 60% (132/222). Among the 170 women with HPV-negative AGC, there was one invasive cervical squamous cell cancer and four HSIL, giving an PPV for a cervical high-grade lesion of 2.9% (5/170). This group also contained five endometrial cancers and one breast cancer.

Conclusions

HPV triaging of AGC will greatly increase the predictive ability for identifying cervical high-grade lesions (OR: 48.4 (95% CI 19.1 to122.6)) and the high sensitivity (96%; 132/137 women) implies safety of primary HPV screening strategies, with regard to this subset of patients. The measurable risk for endometrial cancer among women with HPV-negative AGC (2.9%) suggests that research on screening for endometrial cancer is needed.

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Most cited references 17

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The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study.

Darcey Smith, John M Tiffany, C Qualls … (2000)

The aim of this study was to compare the age-adjusted incidence and survival for invasive adenocarcinoma and squamous cell carcinoma of the uterine cervix using population-based data. The SEER database was used to identify all cases of cervical cancer registered between 1973 and 1996. Stage was defined as localized, regional, or distant. Age-adjusted incidence rates were analyzed statistically using the Jonchkeere-Terpstra exact test for trends. Relative and observed survival rates, respectively, were compared using z tests and log-rank tests. The age-adjusted incidence rates per 100,000 for all invasive cervical cancers decreased by 36.9% over 24 years [12.35 (1973-1977) vs 7.79 (1993-1996)]. Similarly, the age-adjusted incidence rates for squamous cell carcinoma declined by 41.9% [9.45 (1973-1977) vs 5.49 (1993-1996)]. In contrast, the age-adjusted incidence rates for adenocarcinoma increased by 29.1% [1.34 (1973-1977) vs 1.73 (1993-1996)]. The proportion of adenocarcinoma increased 107.4% relative to all cervical cancer, 95.2% relative to squamous cell carcinoma, and 49.3% relative to the population of women at risk [10. 8% vs 22.4% (P < 0.001), 12.4% vs 24.0% (P < 0.001), and 1.40 vs 2. 09 per 100,000 women (P < 0.001), respectively]. Observed survival rates for adenocarcinoma vs squamous cell carcinoma were poorer for regional (P = 0.04), but not localized or distant disease. Over the past 24 years, the incidence of all cervical cancer and squamous cell carcinoma has continued to decline. However, the proportion of adenocarcinoma relative to squamous cell carcinoma and to all cervical cancers has doubled, and the rate of adenocarcinoma per population at risk has also increased. These results suggest that current screening practices in the United States are insufficient to detect a significant proportion of adenocarcinoma precursor lesions. Copyright 2000 Academic Press.

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Screening and cervical cancer cure: population based cohort study

Bengt Andrae, Therese Andersson, Paul Lambert … (2012)

Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden. Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. Results In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%). Conclusions Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions.

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Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival.

Mark E. Sherman, Sophia Wang, Joseph Carreon … (2005)

In the United States, detection of squamous carcinoma in situ (CIS) by screening has led to reduced rates for invasive squamous carcinoma and lower mortality. Adenocarcinoma in situ (AIS) rates also have increased, but invasive cervical adenocarcinoma rates have not declined similarly. To make inferences about the effectiveness of screening, the authors assessed mortality trends for squamous and adenocarcinoma in relation to incidence of these tumors, incidence of their precursors and survival. Using data from the Surveillance, Epidemiology, and End Results program (SEER), the authors tabulated incidence per 10(5) woman-years for invasive carcinomas (1976-2000) and for CIS and AIS (1976-1995) by age ( or = 50 years) and race (whites, blacks). Cumulative relative survival rates were tabulated for 1976-1995 and mortality rates were estimated for 1986-2000. Among all groups, CIS rates approximately doubled whereas rates for invasive squamous carcinoma declined. Among younger whites, mortality declined from 1.12 to 0.93, and for older whites, mortality decreased from 5.02 to 3.82. Among younger blacks, mortality for squamous carcinoma decreased from 2.69 to 1.96. Among older blacks, the mortality rates declined from 14.88 to 9.15. Although AIS rates have increased dramatically among whites (all ages) and younger blacks, adenocarcinoma incidence and mortality rates have not changed greatly. Survival for patients did not change greatly within these age-race groups. The authors concluded that increases in CIS seemed disproportionately large compared with improvements in mortality rates for squamous carcinoma. Despite increased reporting of AIS, declines in mortality for cervical adenocarcinoma have not been demonstrated conclusively. However, future analyses are required to evaluate these trends more completely.

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2017

Publication date (Electronic): 14 December 2017

Volume: 7

Issue: 12

Electronic Location Identifier: e017070

Affiliations

[1 ]departmentDepartment of Clinical Pathology and Cytology , Karolinska University Laboratory, Karolinska University Hospital , Stockholm, Sweden

[2 ]departmentDepartment of Laboratory Medicine , Karolinska Institutet , Stockholm, Sweden

Author notes

[Correspondence to ] Dr Ingrid Norman; ingrid.norman@ 123456ki.se

Article

Publisher ID: bmjopen-2017-017070

DOI: 10.1136/bmjopen-2017-017070

PMC ID: 5735403

PubMed ID: 29247086

SO-VID: a08c4f96-7234-4c8e-afb6-2c9bf552cfa0

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

History

Date received : 31 March 2017

Date revision received : 19 October 2017

Date accepted : 31 October 2017

Funding

Funded by: Stockholm County Clinical Reseearch;

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ScienceOpen disciplines: Medicine

Keywords: cytopathology,epidemiology,gynaecology

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ScienceOpen disciplines: Medicine

Keywords: cytopathology, epidemiology, gynaecology

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Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study

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Abstract

Objectives

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Setting

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Results

Conclusions

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Gamma Delta T cells

Most cited references 17

The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study.

Screening and cervical cancer cure: population based cohort study

Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival.

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