Title: Cervical cancer screening: Comparative study of human papillomavirus detection
between cervical cytology and urine samples
Version: 0 Date: 24 Sep 2024
Reviewer:  Sveinung Wergeland Sørbye
Reviewer's report:
Song et al. have investigated the diagnostic value of HPV-testing using urine samples to
detect women with high-grade cervical lesions (CIN2+). Their study, conducted at the Beijing
Obstetrics and Gynecology Hospital affiliated with Capital Medical University from December
2017 to March 2022, included 458 women with abnormal cytology and/or a positive HPV-test
referred to colposcopy and biopsy. The HPV positivity rate was 79.0% (362/458) using urine
samples and 83.6% (383/458) using cervical cytology, with a high agreement between the two
sample methods (kappa value of 0.7644, P<0.01). Particularly, the detection of the HPV types
16, 52, 18, 33, and 31 demonstrated good correlation between urine and cervical cytology. Of the
458 women, 122 (26.6%) had histologically confirmed CIN2+. The sensitivity of HPV-testing
for CIN2+ was 85.2% (104/122) in urine samples and 88.5% (108/122) in cervical cytology
samples. The study concludes that urine-based HPV-testing for cervical cancer screening is a
viable, simple, and non-invasive alternative to cervical cytology, showing high diagnostic value.
Comments
1. Although the primary objective of cervical cancer screening is to reduce the incidence and
mortality of cervical cancer, the gold standard in studies evaluating cervical cancer screening
should be histologically confirmed high-grade lesions (CIN2+ or CIN3+), not cervical cytology.
Cervical cytology and HPV-testing of cervical samples are screening methods, not diagnostic
standards. Therefore, the sensitivity of HPV-testing in urine samples should be assessed based
on the detection of CIN2+ lesions rather than compared to cervical cytology results. While it is
appropriate to evaluate the correlation between HPV positivity in cervical cytology and urine
samples, sensitivity and specificity should not be calculated using one screening method as the
reference standard for the other.
2. The study's core results regarding CIN2+ are valid, and the conclusion is generally acceptable.
However, the abstract, introduction, materials and methods, most figures and tables, and the
discussion require extensive revision. The title also needs modification. If the manuscript has
undergone copy-editing by a native English speaker, it appears that the editor lacked sufficient
knowledge of HPV-testing and cervical cancer screening, impacting the clarity and accuracy
of the content.
3. Given that the total study population consists of 458 women, all 2×2 contingency tables should
sum up to this total when all cells are counted. However, in Table 1, the total adds up to 455
instead of 458, which requires clarification.
Furthermore, when comparing HPV-testing of urine samples with HPV-testing of cervical
cytology samples, it is misleading to present sensitivity and specificity without referencing
the gold standard—histologically confirmed high-grade lesions (CIN2+). Using one screening
method as the reference standard for another can result in inaccurate assessments. Sensitivity
and specificity should be calculated based on the detection of CIN2+ lesions, not merely on
comparisons between two different screening tests.
4. Table 4 requires restructuring into two separate 2 x 2 tables: one comparing HPV-testing in
cervical cytology versus the detection of CIN2+, and another comparing HPV-testing using urine
samples versus the detection of CIN2+. Additionally, there are discrepancies in the numbers
reported in the table. It appears that the number of HPV positive cervical cytology samples is
incorrectly reported as 25.8% (118/458), suggesting that only 8 of the women without CIN2+
had a positive HPV-test, which incorrectly calculates the specificity as 97.0%. In fact, the correct
number of HPV positive cervical samples is 79.0% (362/458), with 265 women without CIN2+
testing positive, resulting in a specificity of 21.1%.
Similarly, the number of HPV positives using urine samples is misreported as 22.7% (104/458).
This erroneously suggests that only 9 women without CIN2+ had a positive HPV-test, giving an
incorrect specificity of 97.9%. The actual number should be 83.6% (383/458), with 258 women
without CIN2+ testing positive, leading to a specificity of 23.2%.
HPV-test in cervical cytology:
Histology results
CIN2+       CIN1-       Total
HPV in cytology
HPV+             118         265         383
HPV-             4           71          75
Total            122         336         458
Sensitivity: 96.7%
Specificity: 21.1%
Positive Predictive Value (PPV): 30.8%
Negative Predictive Value (NPV): 94.7%
HPV-test in urine sampels:
Histology results
CIN2+       CIN1-       Total
HPV in urine samples
HPV+             104         258         362
HPV-             18          78          96
Total            122         336         458
Sensitivity: 85.2%
Specificity: 23.2%
Positive Predictive Value (PPV): 28.7%
Negative Predictive Value (NPV): 81.3%
5. The ROC curves in Figures 1, 3, and 5, which compare sensitivity and specificity of HPV
testing in urine to HPV testing in cervical cytology, are misleading. Using cervical cytology
as a gold standard in this context is inappropriate as it is not a diagnostic standard for cervical
precancerous lesions. These figures should be removed to prevent misinterpretation.
6. Many of the references cited in the manuscript are unfamiliar to me, and they appear to be
secondary sources that rely on information from other primary studies. To ensure scientific
accuracy, it is essential that the manuscript directly cites the original primary references.
7. 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.
8. In the manuscript, the authors have presented percentages with two decimal places. For ease
of reading and to simplify the presentation in both tables and text, I recommend rounding these
percentages to one decimal place (e.g., 83.62% to 83.6%).
9. Delete this paragraph in the results section:
"Based on the severity of pathogenicity and the proportion of positive typing, three types of
HPV16, HPV52, and HPV18 with higher pathogenicity and positivity were selected to analyze
the consistency between urine standards and cervical specimen testing
Among the 458 vaginal biopsy specimens, 122 are positive (#CIN2), accounting for 26.64%. In
the HPV16 cervical cell test, 109 cases are positive, with a sensitivity of 81.97%, a specificity
of 97.32%, and a 95%CI (0.865-0.9923). 110 cases are positive in urine sample testing, with
sensitivity of 82.79%, specificity of 97.02%, and 95% CI (0.868-0.925).In the HPV52 cervical
cell test, 83 cases are positive, with a sensitivity of 59.02%, a specificity of 96.73%, and a
95%CI (0.868-0.925). 76 urine samples are positive, with a sensitivity of 57.38%, a specificity
of 97.62%, and a 95%CI (0.738-0.816).There are 51 positive cases in the HPV18 cervical cell
test, with a sensitivity of 32.79%, a specificity of 96.37%, and a 95%CI (0.602-0.691). 49 urine
samples are positive. The sensitivity is 36.89%, the specificity is 98.81%, and the95%CI is
(0.634~0.721). They have no difference in sensitivity between urine test and cervical cell test
(P>0.05), (Table 5 and Fig 5). "
Terminology: The term "higher pathogenicity" is used to describe the HPV types. This could be
misleading as it suggests a comparative risk level that is not universally applicable outside the
context of oncogenic potential relative to cervical cancer. It may be more accurate to discuss the
oncogenic potential relative to their prevalence in causing cervical cancer.
Statistical Accuracy: The paragraph presents sensitivity and specificity values that significantly
deviate from those calculated from the 2 x 2 tables presented earlier in the manuscript. For
example, the reported high specificity for both testing methods contradicts the substantially
lower specificity figures (around 21% and 23%) derived from the 2 x 2 tables. This discrepancy
could mislead readers and detract from the study’s credibility.
Relevance of Positivity Rates: The focus on positivity rates for HPV types in the context of their
prevalence in cervical cancer is more clinically relevant than their general positivity rates in the
population. The current discussion might confuse readers about the study's aims and the clinical
implications of the findings.
Major revisions
Title,  "Cervical Cancer Screening: A Comparative Study of HPV Testing in Cervical Cytology
versus Urine Samples"
Abstract, "Objective: To evaluate the utility of urine-based HPV testing in detecting high-grade
cervical lesions (CIN2+) compared to cervical cytology.
Methods: This study retrospectively analyzed data from 458 patients with abnormal cytology
and/or a positive HPV test, collected at Beijing Obstetrics and Gynecology Hospital, affiliated
with Capital Medical University, from December 1, 2017, to March 31, 2022. Patients were
tested for HPV using both cervical cytology and urine samples, with outcomes correlated to
cervical biopsy results.
Results: HPV was detected in 383 cervical cytology samples (83.6%) and 362 urine samples
(79.0%). Cervical biopsies confirmed 122 cases (26.6%) as CIN2+. The sensitivity for detecting
CIN2+ lesions was 96.7% using cervical cytology and 85.2% using urine testing, with
specificities of 21.1% and 23.2%, respectively. The kappa value indicating agreement between
urine and cervical cytology HPV tests was 0.764 (P<0.01), demonstrating high correlation.
Among various HPV types, HPV16, HPV52, and HPV18 showed high prevalence, with no
significant difference in detection rates between urine and cervical cytology for these types
(P>0.05).
Conclusion: Urine HPV testing demonstrates promising results as a non-invasive screening
option, showing strong agreement with cervical cytology and potentially increasing compliance
among women reluctant to undergo more invasive gynecological examinations. This method
simplifies the screening process and holds significant potential in enhancing cervical cancer
prevention strategies."
Background,  "Cervical cancer remains a significant global health issue, primarily driven by
infection with high-risk subtypes of the Human Papillomavirus (HPV). Epidemiological studies
indicate that approximately 80% of sexually active women will acquire an HPV infection at some
point in their lives, with around 10% developing persistent infections that may lead to cervical
precancerous lesions or cancer. Globally, cervical cancer is the fourth most common cancer
among women, with an estimated 604,000 new cases and 342,000 deaths reported in 2020. The
burden of disease is disproportionately high in less developed regions, where limited access to
effective screening and preventive measures contributes to rising incidence rates and mortality,
particularly among younger populations. These statistics underscore the critical importance of
cervical cancer screening programs, which are pivotal in reducing the incidence and mortality
associated with the disease.
The primary etiological factor for cervical cancer is persistent infection with high-risk Human
Papillomavirus (HPV) types, underscoring the importance of detecting these viruses as a
cornerstone of cervical cancer screening. Conventional Pap cytology, once the standard, offers
a sensitivity of only about 65% for detecting high-grade cervical lesions (CIN2+). In contrast,
the second-generation hybrid capture assay (HC2) demonstrates enhanced performance with a
sensitivity of 96.0% and specificity of 90.5% for identifying high-risk HPV infections. High-
risk HPV types, including HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51,
HPV52, HPV56, HPV58, and HPV59, are strongly associated with the risk of developing
cervical cancer. In China, HPV DNA tests employing real-time fluorescence quantitative PCR
technology are utilized to accurately detect and differentiate various HPV genotypes, crucial
for risk assessment and management of cervical lesions. Despite the effectiveness of HPV
screening and genotyping, barriers such as lack of access to healthcare services or awareness
can lead some women to miss early diagnoses, delaying treatment and adversely affecting
outcomes. Consequently, adopting screening methods that are simple, convenient, and patient-
friendly is vital for enhancing early detection rates of precancerous conditions, facilitating timely
intervention, and improving disease prognosis.
The epithelial tissue of the cervix, characterized by a thin layer of squamous cells prone
to continuous shedding, undergoes increased turnover following HPV infection. Shed cells
and cervical secretions accumulate around the vaginal opening and the labia minora. During
urination, the flow of urine washes away these cells and secretions, enabling the detection
of HPV in urine samples. Research has shown high diagnostic concordance between urine
and cervical samples, with urine testing offering a non-invasive advantage. This method is
particularly beneficial when conventional screening methods are impractical or invasive. Urine
samples can be self-collected, providing simplicity, enhanced privacy, and flexibility in timing
and location. This improves screening compliance in remote or underserved areas, where
logistical constraints, traditional beliefs, or work schedules may restrict access to healthcare.
With the advancement of digital health, home urine sampling is becoming a promising direction
for cervical cancer screening, enhancing patient engagement in early disease detection. This
study includes 458 women with abnormal cytology and/or a positive HPV-test, all meeting the
criteria for diagnostic colposcopy and biopsy, to evaluate the utility and relevance of urine-based
HPV testing in screening and detecting high-grade lesions (CIN2+)."
Material and Methods,  "Research Materials
This study utilized cervical cell and urine samples from 458 women aged 20-60 years (mean age
45.2 ± 10.6 years), who presented with suspected cervical precancerous lesions and underwent
colposcopy and HPV biopsy at Beijing Maternity Hospital, affiliated with Capital Medical
University. All participants had indications for colposcopy biopsy based on their clinical
presentation.
Inclusion and Exclusion Criteria
Participants included in the study were required to have an intact uterus, show evidence
of abnormal cervical cytology or a positive test for high-risk HPV, and present symptoms
of vaginal discharge and bleeding of undetermined origin. They were also required to have
adequate cognitive and mental health status to provide informed consent and comply with study
procedures. Individuals were excluded from the study if they were suspected of being pregnant,
had a history of cervical surgery or treatment, had undergone a hysterectomy for gynecological
conditions, were diagnosed with bladder, ureteral, or renal cancer, or had previously received
pelvic radiation therapy.
Research Methods
Urine Sample Collection and HPV Testing
1. Urine Sampling: Patients were instructed to refrain from sexual activity for 72 hours prior to
sample collection, avoid vaginal douching or medication, and ensure they were not experiencing
vaginal bleeding. A sterile urine collection device containing 7mL of storage solution was used
to collect 10mL of the first morning urine or the first urine after 1 hour of non-urination. The
sample was then placed in the device for testing.
2. Urine Specimen Preservation: The collected urine was mixed thoroughly with a buffer
solution, filtered, and then centrifuged for 20 minutes to obtain a concentrated solution. Each
patient's specimen was divided into three aliquots and stored at room temperature, 4#, and
-20# respectively. Preliminary experiments were conducted randomly on these three aliquots
to extract HPV DNA from the urine using the centrifugation column method. The sample
qualification rate was assessed across different storage temperatures, with a success rate of 100%
and no significant difference in test results among the three temperatures. The specimens were
then maintained in the laboratory at 4# and -20# for further analysis.
3. Urine Sample HPV Test: For HPV testing, the stored urine sample was processed to remove
the supernatant using the centrifuge column method. To each 1mL of sample, 20µl of protease
K20 was added and mixed thoroughly. Subsequently, 200µl of cell lysis buffer was added and
mixed evenly using a shaking method. The sample solution was then incubated in a 56# bath for
15-20 minutes, after which 200µl of anhydrous ethanol was added. The mixture was transferred
to a centrifuge tube fitted with a silica gel column and centrifuged at 1000rpm for 1 minute.
The flow-through was discarded, and 500µl of cell lysis buffers W1, W2, and W2 were added
sequentially into the silica gel column, centrifuging each time at the same speed and duration.
After discarding the final flow-through, the empty tube was centrifuged at 12000rpm for 3
minutes. The gel column was then placed in the tube, left open to air-dry for 1-2 minutes, and
eluted with TE buffer. The column was allowed to stand for 2-5 minutes before centrifugation at
12000rpm for 2 minutes. The column was discarded, and the eluate, containing the HPV DNA
from the tissue, was collected for analysis.
Cervical Cell Sample Collection and HPV Detection
1. Sample Collection and Preservation: Cervical cells are collected at the bladder lithotomy site
using a cervical exfoliated cell collector and immediately placed into a cell preservation solution.
Samples are stored at 4# if they are to be tested within two weeks, and at -20# for tests conducted
within six months.
2. HPV Testing of Cervical Samples: To prepare for testing, 2ml of the cervical exfoliated cell
sample is centrifuged at 13,000 rpm for 1 minute to separate the supernatant, which is then
discarded. Next, 0.5ml of the sample cell preservation solution is added and mixed thoroughly,
followed by another centrifugation at 13,000 rpm for 1 minute. After discarding the supernatant,
50µl of cell lysate is added to the sample, which is then shaken, mixed, and boiled for 10
minutes. The sample is then centrifuged at 13,000 rpm for 10 minutes to collect the supernatant
for subsequent analysis. Using a reagent kit equipped with amplification reagents, the sample
undergoes a final centrifugation at 8,000 rpm for 10 seconds. For the PCR reaction, 18µl of
amplification reagent is combined with 2µl of the DNA sample in a reaction tube, lightly
centrifuged, and then transferred to a fluorescent PCR detection instrument for analysis.
Colposcopy and Cervical Biopsy
Prior to the examination, patients are instructed on the procedure and positioned in the bladder
lithotomy position. The examination involves assessing the perianal area, external genitalia,
vagina, cervix, and secretions. Lesions are identified using 3-5% acetic acid staining. During the
colposcopy, areas with significant lesions on the cervix are selected for biopsy using forceps.
If necessary, scraping of the cervical area may also be performed to obtain additional samples
from the external genital tissues. Routine biopsies are conducted at the 3, 6, 9, and 12 o'clock
positions of the cervix when no suspicious lesions are observed, and the specimens are sent for
pathological examination.
Detection Methods for Various Types of HPV Typing in Cervix and Urine
HPV DNA samples from the cervix and urine are analyzed for multiple HPV types using
polymerase chain reaction (PCR) amplification. The types tested include HPV16, HPV58,
HPV52, HPV53, HPV56, HPV66, HPV18, HPV42, HPV81, HPV33, HPV51, HPV68, HPV59,
HPV39, HPV44, HPV43, and HPV31.
Data Statistics and Analysis
Data were processed and analyzed using SPSS software, version 26.0. Categorical data are
presented as the number of cases (n) and percentages (%). Intergroup comparisons were
conducted using the chi-square (#2) test. Diagnostic criteria were based on the HPV test
results from cervical cells and colposcopy tissue biopsies. The sensitivity, specificity, and 95%
confidence intervals (CIs) of the HPV test in urine samples were evaluated using Receiver
Operating Characteristic (ROC) curve analysis. Consistency between the detection results from
urine samples, cervical cell samples, and colposcopy tissue biopsies was assessed using Kappa
analysis. The Kappa values were interpreted as follows: less than 0 indicated poor consistency,
0 to 0.20 slight consistency, 0.21 to 0.40 weak consistency, 0.41 to 0.60 moderate consistency,
0.61 to 0.80 strong consistency, and 0.81 to 1.00 very strong consistency. A p-value less than
0.05 was considered statistically significant.
Results, "Out of the 458 specimens analyzed, the HPV positivity rate was 83.6% (383/458)
using cervical cytology and 79.0% (362/458) using urine samples. The data revealed strong
concordance between cervical cytology and urine sample testing. Specifically, 359 cases were
positive in both tests, and 69 cases were negative in both, totaling 428 specimens with consistent
HPV results across both methods. This results in a detection accuracy rate of 93.4%. The high
agreement between the two sample methods is underscored by a kappa value of 0.7644 (P<0.01),
as presented in Table 1.
Different HPV subtypes were analyzed in 458 cervical cell specimens, with prevalence rates
for each subtype presented in Table 2. The most prevalent subtypes in cervical samples
included HPV16, HPV58, and HPV52, reflecting the expected subtype distribution in China.
The detection rates of these subtypes in urine samples were generally slightly higher for HPV16
and HPV58, along with some other high-risk subtypes, underscoring the sensitivity of urine-
based testing. The analysis revealed a comparable distribution of subtypes between cervical and
urine samples, with HPV44 maintaining a consistent positive rate of 3.9% across both methods.
These findings suggest that urine testing can effectively mirror the subtype distribution observed
in cervical cytology, supporting its potential utility in non-invasive HPV screening.
An analysis was conducted on five disease subtypes targeted by the HPV nine-valent vaccine to
evaluate the diagnostic utility of urine testing and its consistency with HPV testing in cervical
cytology. The kappa values were 0.850 for HPV16 (P<0.01), 0.827 for HPV52 (P<0.01), 0.753
for HPV18 (P<0.01), 0.699 for HPV33 (P<0.01), and 0.599 for HPV31 (P<0.01). These findings,
detailed in Table 3, demonstrate significant agreement between urine and cervical cytology HPV
tests, validating the use of urine testing for HPV detection.
Diagnostic Evaluation of HPV Testing Using Cervical Biopsy as the Gold Standard
Among 458 samples, 122 (26.6%) were histologically confirmed as CIN2+ through cervical
biopsy. For cervical cytology, 118 cases tested HPV positive, yielding a diagnostic sensitivity of
96.7% (118/122) and a specificity of 21.1% (71/336). For urine samples, 104 cases tested HPV
positive. The diagnostic sensitivity for these was 85.2% (104/122), with a specificity of 23.2%
(78/336). The sensitivity of HPV detection in cervical cytology is statistically higher than in
urine samples (P<0.05), indicating a significant difference in diagnostic effectiveness between
the two methods. These results are comprehensively detailed in Table 4.
Discussion,  "The Role of HPV Testing in Urine Samples for Detection of High-Grade Lesions
(CIN2+)
Screening with HPV testing is pivotal in identifying women at elevated risk of developing
cervical precancerous lesions. HPV testing, a well-established component in cervical cancer
research, traditionally involves clinician-collected cervical cytology using a brush. This method
can be invasive, creating barriers such as discomfort or embarrassment, which may lead to
lower compliance with screening programs. Additionally, logistical issues such as transportation
and complex procedural requirements further hinder participation, particularly among women
lacking awareness of cervical cancer risks.
Despite its critical role in screening programs, HPV testing is not a standalone diagnostic tool
for cervical cancer. Accurate diagnosis typically requires a triage process involving cervical
cytology followed by colposcopy and biopsy if high-risk HPV types are detected or if cytology
results are abnormal. This pathway ensures that high-grade lesions (CIN2+) are identified and
treated early to prevent the development of cervical cancer.
Recent studies highlight the potential of urine-based HPV testing as a non-invasive alternative
that could address some of these barriers. For instance, Van Keer S et al. reported that urine HPV
testing might offer comparable sensitivity and specificity to traditional cervical cytology when
early morning samples are used and proper preventive measures are implemented during the
collection and DNA testing processes. Furthermore, research by John JH et al. on self-collected
urine and vaginal samples from pregnant women showed high agreement in HPV detection
between the two methods, evidenced by substantial kappa values. These findings suggest that
urine HPV testing could be an effective screening tool, providing a less invasive option that
may increase compliance among women hesitant about traditional methods, thereby ensuring
broader participation in screening programs.
Urine HPV testing holds significant potential in enhancing the detection of cervical precancerous
conditions, contributing to early intervention strategies crucial for reducing the incidence and
mortality of cervical cancer.
Concordance Between HPV Testing in Urine Samples and Cervical Cytology
The analysis of 458 specimens revealed that 383 (83.6%) tested HPV positive in cervical
cytology, while 362 (79.0%) were HPV positive in urine samples. This data demonstrates a
high degree of concordance between the two methods, with a kappa value of 0.764 (P<0.01),
indicating strong correlation. This significant alignment is especially noteworthy for the HPV
subtypes targeted by the nine-valent vaccine, crucial in the context of cervical cancer prevention.
Previous studies, such as those by Hantre-Justino M et al., have reported similar findings, where
early morning urine samples from HPV-positive patients showed high concordance with cervical
cytology results. These findings highlight the potential of urine testing as not only a screening
tool but also a more acceptable and less invasive method for ongoing monitoring, particularly
in populations with low compliance to traditional cervical screening methods.
The non-invasive nature of urine sampling can significantly enhance patient compliance
and coverage, especially among women who are hesitant about more invasive procedures.
Additionally, the capability for women to self-collect urine samples as medically advised allows
for greater flexibility and accessibility in screening programs. Considering that HPV infection
progression is influenced by factors including immune response, broader screening coverage
can facilitate earlier identification and management of high-risk cases, potentially preventing
the progression to cervical cancer.
Comparative Efficacy of Urine and Cervical Cytology HPV Testing Relative to Cervical Biopsy
Standards
With cervical biopsy as the diagnostic standard, this study analyzed the diagnostic efficacy
of both urine and cervical cell samples. Out of 458 specimens, 122 (26.6%) were confirmed
as CIN2+ via cervical biopsy. Urine samples identified 104 HPV positive cases, yielding a
diagnostic sensitivity of 85.2% and a specificity of 23.2%. When analyzing some important high-
risk HPV types such as HPV16, HPV52, and HPV18, no statistically significant differences were
found in sensitivity and specificity between urine and cervical cell samples (P>0.05), indicating
comparable efficacy. Punyashthira A et al. [reference] have suggested that self-collected urine
for HPV testing is a viable alternative, especially in scenarios where HPV vaccination influences
prevalence rates."
Conclusions, "Urine HPV testing offers a valuable complement to cervical cytology by
addressing some of its limitations, particularly its invasiveness. While the sensitivity of urine-
based HPV testing may be slightly lower than that of cervical samples, it remains a viable
screening option. The non-invasive nature of urine testing significantly enhances patient
acceptance and compliance, thereby increasing the potential reach and impact of HPV screening
programs. By incorporating urine HPV testing into the existing cervical cancer prevention and
control framework, it is possible to improve overall screening rates and subsequently enhance
the effectiveness of preventive measures against cervical cancer."