Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum

Abstract

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n ‫؍‬ 48), CIN 2 (n ‫؍‬ 60), CIN 1 (n ‫؍‬ 58), or condyloma acuminatum (CAC) (n ‫؍‬ 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases.Cervical cancer (CC) is the second most common malignancy and cause of cancer-related death in women worldwide (17). The well-defined premalignant phase of this cancer has contributed to the success of the cytology-based Papanicolaou (Pap) screening test; the incidence of CC in resource-rich countries has been dramatically reduced by the use of this test (11). However, the Pap test has several limitations: (i) the collection of cervical cells can create discomfort and embarrassment (7); (ii) evaluation of test results in cytology screening involves subjective assessments with high susceptibility to intraindividual and interindividual variability (11); (iii) the test exhibits low (around 51%) sensitivity for detection of highgrade (HG) cervical intraepithelial neoplasia (HGCIN) (11); and (iv) cytology-trained personnel and special equipment with excellent quality control are needed, which involves a huge amount of resources (3). Therefore, there is a need for another cervical screening test that can overcome these limitations. Recent studies have shown that the human papillomavirus (HPV) DNA test is more sensitive than the Pap test in detecting HGCIN (11-13). However, the sample collection method, using a cytobrush, is still invasive and unpleasant, which would affect a woman's decision whether to take the Pap test. We hypothesized that menstrual blood (MB) collected in sani...

Detection of high‐risk human papillomavirus using menstrual blood in women with high‐grade squamous intraepithelial lesions or high‐risk human papillomavirus infections: A pilot study

“…Additionally, in a study involving a general population of patients who visited clinics for routine examinations, the HPV tests using MB and clinician‐performed cervical HPV tests had 97.8% agreement for the detection of HPVs . Although previous investigators have reported a high agreement rate for detecting HR‐HPVs from cervical and MB samples, they did not target HR‐HPVs or the studies were performed in a case–control setting . In contrast to previous studies, we were able to provide data regarding the detection of HR‐HPV in MB, especially in patients with CIN 2, 3 and cancer, according to MCD, in a prospective cohort setting (Table and ).…”

“…According to the analysis of MB collected from the sanitary pads, MB HR‐HPV DNA was detected in 89.8% of HPV DNA‐positive women with CIN 2 and CIN 3 and 26.7% of HPV DNA‐positive women with CIN 1 or condyloma acuminatum . Additionally, in a study involving a general population of patients who visited clinics for routine examinations, the HPV tests using MB and clinician‐performed cervical HPV tests had 97.8% agreement for the detection of HPVs .…”

“…Patient‐performed HPV screening tests are inconvenient for collection, storage and delivery of specimens within liquid media. Only a few studies have reported the detection of HPVs in menstrual blood (MB) using a sanitary pad . Pads can more conveniently be enclosed in a Ziploc bag and sent to the laboratory by mail .…”

“…Only a few studies have reported the detection of HPVs in menstrual blood (MB) using a sanitary pad. [7][8][9] Pads can more conveniently be enclosed in a Ziploc bag and sent to the laboratory by mail. 7,8 MB HPV DNA was reported to have a sensitivity and specificity of 82.8% and 93.1%, respectively, for CIN or condyloma acuminatum.…”

“…[7][8][9] Pads can more conveniently be enclosed in a Ziploc bag and sent to the laboratory by mail. 7,8 MB HPV DNA was reported to have a sensitivity and specificity of 82.8% and 93.1%, respectively, for CIN or condyloma acuminatum. 8 In another study, MB HPV DNA was observed to have a sensitivity of 76.9% and specificity of 93.3% for CIN, which was similar to that for CIN 2 or CIN 3.…”