Title: Cervical cancer screening: Comparative study of human papillomavirus detection
between cervical cytology and urine samples
Version: 3 Date: 09 Jan 2025
Reviewer:  Sveinung Wergeland Sørbye
Reviewer's report:
1. The authors have effectively addressed the reviewers' comments in their revised manuscript.
However, there seem to be inaccuracies in the calculation of the HPV positivity rate for cervical
cytology samples.
Cervical Cytology HPV Positivity Rate:
From Table 4:
Cervix HPV Positive = 118 (CIN2+ positive) + 268 (CIN2+ negative) = 386
Total specimens = 458
HPV positivity rate in cervical cytology = (386 / 458) × 100 # 84.3%
Urine Sample HPV Positivity Rate:
From Table 4:
Urine HPV Positive = 104 (CIN2+ positive) + 258 (CIN2+ negative) = 362
Total specimens = 458
HPV positivity rate in urine samples = (362 / 458) × 100 # 79.0%
2. I recommend using the following revised text based on the data in Table 4:
"Among 458 specimens, the HPV positivity rate in cervical cytology was 84.3% (386/458), with
a sensitivity of 96.7%, specificity of 20.2%, positive predictive value of 30.6%, and negative
predictive value (NPV) of 94.4% (P<0.01). The HPV positivity rate in urine samples was 79.0%
(362/458), with a sensitivity of 85.2%, specificity of 23.2%, positive predictive value of 28.7%,
and negative predictive value (NPV) of 81.2% (P<0.01), as shown in Table 4."
3. I recommend using the following revised abstract:
"Objective: To evaluate the efficacy of urine-based human papillomavirus detection in detecting
high-grade cervical lesions (CIN2+) compared to cervical cytology examination.
Method: The data of 458 patients with cytological abnormalities and/or positive human
papillomavirus test results were retrospectively selected from December 1, 2017, to March
31, 2022, at the Beijing Obstetrics and Gynecology Hospital affiliated with Capital Medical
University. Cervical cytology and urine samples were used to detect human papillomavirus
status and analyze the correlation between the results and cervical biopsy results.
Results: Among the selected 458 samples, 386 were positive for human papillomavirus through
cervical cytology examination, with a detection rate of 84.3%. Out of 458 urine samples, 362
were positive, with a detection rate of 79.0%. The data shows a high consistency between
cervical cytology and urine sample testing, with a kappa value of 0.637 (P<0.01). The
most prevalent subtypes in cervical samples included HPV16, HPV58, and HPV52, while
the detection rates of HPV16 and HPV58 subtypes were relatively high in urine samples.
The comparison of subtype distribution between cervical and urine samples showed that the
positivity rate of HPV44 subtype was consistent, both at 3.9%. Among the five HPV subtypes
corresponding to the HPV nine-valent vaccine, the kappa value of HPV16 in cervical and
urine samples was 0.791 (P<0.05), the kappa value of HPV52 was 0.766 (P<0.05), HPV18
was 0.762 (P<0.05), HPV33 was 0.539 (P<0.01), and HPV31 was 0.458 (P<0.05). Among 458
specimens, the sensitivity of human papillomavirus detection in cervical cytology was 96.7%,
with a specificity of 20.2% (P<0.01). The sensitivity of human papillomavirus detection in urine
samples was 85.2%, with a specificity of 23.2% (P<0.01).
Conclusion: Urine human papillomavirus testing, as a non-invasive screening method, has
significant application effects. The screening results are highly consistent with cervical cytology
screening and may improve the compliance of women who do not want to undergo invasive
gynecological examinations. This screening method simplifies the screening process and has
great potential in screening cancer lesions and preventing cervical cancer."
4. Please ensure standard formatting is used for degrees Celsius in the text. Here’s the revised
version:
"Urine sample preservation: Mix the collected urine thoroughly with buffer solution, filter, and
centrifuge for 20 minutes to obtain a concentrated solution. Divide each patient's sample into
three equal parts and store them at room temperature or at -20°C. Randomly conduct preliminary
experiments on these three aliquots to extract HPV DNA from urine using a centrifugal column
method. Evaluate the sample qualification rate, achieving a success rate of 100%. Then, store
the sample in a laboratory at -20°C for further analysis."
5. Please ensure standard formatting is used for degrees Celsius in the text. Here’s the revised
version:
"Cervical cell sample collection and HPV detection
Sample collection and preservation: Collect cervical cells using a cervical exfoliated cell
collector at the bladder stone removal site and immediately place them in a cell preservation
solution. If the sample is to be tested within two weeks, it should be stored at 4°C. If tested
within six months, it should be stored at -20°C."
6. Missing space: "Results The consistency analysisbetween cervical cell sample detection and
urine sample detection" => "Results The consistency analysis between cervical cell sample
detection and urine sample detection"
7. Missing space: "Positive cases of HPV analysisin cervical specimens of different types" =>
"Positive cases of HPV analysis in cervical specimens of different types"
8. "Table 3 Consistency of cervical cell sample testing and urine testing for 5 HPV subtypes
corresponding to HPV virus nine valent vaccine" => "Table 3 Consistency of cervical cell sample
testing and urine testing for five HPV subtypes corresponding to the nine-valent HPV vaccine"
9. Discussion "The role of HPV detection in detecting CIN2+ in urine samples
Cervical cancer ranks as the fourth most common malignancy among women worldwide, posing
a significant public health challenge. Persistent infection with high-risk human papillomavirus
(HPV) is the primary etiological factor for cervical cancer, leading to the development of cervical
intraepithelial neoplasia (CIN) and its progression to invasive cancer. CIN is categorized into
three stages (CIN1, CIN2, and CIN3) based on the degree of epithelial dysplasia. The risk of
progression to cervical cancer varies with different HPV types, with high-risk subtypes being
the predominant contributors. Importantly, studies have highlighted that HPV viral load may
serve as a key indicator of the likelihood of persistent infection and progression to precancerous
or cancerous lesions [17]."
10. Conclusion "HPV testing serves as a valuable complement to cervical cytology screening,
particularly by addressing the limitations of invasive procedures. While the sensitivity of HPV
detection in urine samples is slightly lower than that of cervical samples, it remains a practical
and effective method for early cervical cancer screening. The non-invasive nature of urine
testing greatly enhances patient acceptance and compliance, broadening the reach and impact
of HPV screening programs. Integrating urine-based HPV testing into existing cervical cancer
prevention strategies can substantially increase screening rates, thereby improving the overall
effectiveness of cervical cancer prevention and management efforts."
11. Missing space: Declarations: "Ethics approval and consent to participate
Ethical approval for this study was obtained from Capital Medical University. All experiments
in this study were conducted in accordance with relevant guidelines and regulations, as well as
the Declaration of Helsinki. Written informed consent was obtained from all patients."
12. To ensure accurate and efficient peer reviews and simplify the post-review editing
procedures, it is recommended to use a line numbering system for all submitted manuscripts.