J Gynecol Oncol.  2016 Jan;27(1):e3. 10.3802/jgo.2016.27.e3.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

• Onuki M
• Matsumoto
• Sakurai M
• Ochi H
• Minaguchi
• Satoh T
• Yoshikawa

• KMID: 2360233
• DOI: http://doi.org/10.3802/jgo.2016.27.e3

Abstract

OBJECTIVE
We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3).
METHODS
Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013.
RESULTS
The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001).
CONCLUSION
Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

Keyword

Cell Biology; Cervical Intraepithelial Neoplasia; Human Papillomavirus; Posttreatment Surveillance

MeSH Terms

Cervical Intraepithelial Neoplasia/pathology/surgery/*virology
Female
Humans
Neoplasm Recurrence, Local/*virology
Neoplasm, Residual
Papillomaviridae/*isolation & purification
Papillomavirus Infections/complications/*diagnosis
Predictive Value of Tests
Risk Assessment/methods
Sensitivity and Specificity
Uterine Cervical Neoplasms/pathology/surgery/*virology

Figure

• 

  Fig. 1. Literature search. Initial search through PubMed identified 1,143 articles for our systematic review. After reviews of titles, abstracts and full texts, 33 eligible articles were included in our analysis [10–42]. CIN 2, cervical intraepithelial neoplasia grade 2; HPV, human papillomavirus.

• 

  Fig. 2. Risk stratification of posttreatment cervical intraepithelial neoplasia grade 2+ (CIN 2+) provided by carcinogenic human papillomavirus (HPV) testing, cytology, and surgical margin histology. In each test method of high-risk HPV testing, cytology (atypical squamous cells of undetermined significance+) or surgical margin histology, the absolute risks of having recurrent or residual CIN 2+ lesions (■) and 95% confidence intervals (error bars) were calculated for women testing positive or negative for each test. HPV testing provided the greatest risk stratification between test-positive and -negative women.

• 

  Fig. 3. Further risk stratification of posttreatment cervical intraepithelial neoplasia grade 2+ (CIN 2+) provided by the addition of carcinogenic human papillomavirus (HPV) testing to cytology and surgical margin histology. Carcinogenic HPV testing provided additional risk stratification for posttreatment CIN 2+ lesions according to cytology results (atypical squamous cells of undetermined significance+) or surgical margin status. The absolute risks of having recurrent or residual CIN 2+ lesions and 95% confidence intervals (error bars) were calculated for HPV-positive (■) and -negative women (■) in each category group.

Reference

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