Title: Cervical cancer screening: Comparative study of human papillomavirus detection
between cervical cytology and urine samples
Version: 2 Date: 07 Nov 2024
Reviewer:  Sveinung Wergeland Sørbye
Reviewer's report:
Most of the comments have been addressed adequately, and the responses have improved the
manuscript. However, some issues remain:
1. The numbers in the 2 x 2 table in Table 1 do not match those presented in the text.
In the abstract, it states: 'Results: Among 458 specimens, 386 were HPV-positive cases detected
by cervical cytology, with a detection rate of 84.28%, and 362 were positive cases detected by
urine samples, with a detection rate of 79.0%.'
In Table 1, the HPV positivity rate in urine samples is given as 79.7% (365/458), not 79.0%. If
the total number of HPV-positive cases in urine is indeed 362, and all 362 cases are also HPV-
positive in cervical cytology, then there cannot be any cases where the HPV test is positive in
urine but negative in cervical cytology. Yet, Table 1 reports three such cases, which suggests a
discrepancy that needs to be addressed.
2. When comparing HPV detection in urine and cervical cytology (Table 1 and 3), excluding
histology, only the kappa value is relevant. Presenting sensitivity, specificity, and AUC is not
meaningful in this context. Additionally, the p-value should be reported as P < 0.001 instead
of P = 0.000.
3. There is a discrepancy between the HPV positivity rate and the sensitivity for CIN2+ when
using the HPV test in cervical cytology, as reported in the text versus Table 4. In the text, the HPV
positivity rate for cervical cytology is given as 84.3% (386/458), while in Table 4 it is reported
as 25.8% (118/458). Similarly, the sensitivity for CIN2+ of the HPV test in cervical cytology is
described in the text as 96.7% (118/122), but in Table 4, it is listed as 82.0% (100/122).
Based on the figures provided in the text, the distribution for cervical samples is as follows:
True Positives (TP): 118 (HPV+ and CIN2+)
False Positives (FP): 268 (HPV+ and CIN1-)
False Negatives (FN): 4 (HPV- and CIN2+)
True Negatives (TN): 68 (HPV- and CIN1-)
Resulting metrics:
Sensitivity: 96.7%
Specificity: 20.2%
Positive Predictive Value (PPV): 30.6%
Negative Predictive Value (NPV): 94.4%
Calculating kappa values using the HPV test and histology as the gold standard is not meaningful
in this context.
4. There is a discrepancy between the HPV positivity rate and the sensitivity for CIN2+ when
using the HPV test in urine samples, as reported in the text versus Table 4. In the text, the HPV
positivity rate for urine samples is given as 79.0% (362/458), whereas in Table 4 it is reported
as 22.7% (104/458). Additionally, the sensitivity for CIN2+ of the HPV test in urine samples is
described in the text as 85.2% (104/122), but in Table 4 it is listed as 80.3% (98/122).
Based on the figures provided in the text, the distribution for urine samples is as follows:
- True Positives (TP): 104 (HPV+ and CIN2+)
- False Positives (FP): 258 (HPV+ and CIN1-)
- False Negatives (FN): 18 (HPV- and CIN2+)
- True Negatives (TN): 78 (HPV- and CIN1-)
Resulting metrics:
- Sensitivity: 85.2%
- Specificity: 23.2%
- Positive Predictive Value (PPV): 28.7%
- Negative Predictive Value (NPV): 81.2%
Calculating kappa values using the HPV test and histology as the gold standard is not meaningful
in this context.
5. I recommend that the authors adjust the percentages to one decimal place to enhance the
readability and flow of the manuscript. For instance, changing '84.28%' to '84.3%' simplifies the
information, thereby making it quicker and easier to comprehend at a glance.
Minor revisions
Abstract, Results, "Among 458 samples, 122 cases (26.6%) had cervical biopsy-confirmed
CIN2+. HPV testing of cervical cytology samples identified 118 HPV-positive cases, resulting
in a sensitivity for CIN2+ of 96.7% and a specificity of 20.2%. In urine samples, 104 cases were
HPV-positive, yielding a diagnostic sensitivity for CIN2+ of 85.2% and a specificity of 23.2%."
Background, "In low- and middle-income countries (LMICs), the number of new cases is higher
due to the lack of national cervical cancer screening programs."
Data statistics processing, "The diagnostic criteria are based on the results of HPV detection
through cervical cell and vaginal colposcopy tissue biopsy." => "Histologically confirmed high-
grade lesions (CIN2+) in cervical biopsies were used as the gold standard."