Effectiveness of prophylactic HPV vaccines against cervical abnormalities and HPV infection in Japan: The J-HERS 2021 multicenter study.

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan's first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Preferential Tissue Sites of Different Cancer-Risk Groups of Human Papillomaviruses.

The oncogenic potential of human papillomavirus (HPV) may be used to determine the tissue tropism of each HPV type. Cervical cancer develops in the squamo-columar junction of the cervices, and most lesions are induced by high-risk (HR) HPV types. This suggests that HR types preferentially infect the cervix, whereas the preferential infection site for low-risk (LR) types is not well defined. The determination of HPV tropism when using cytology samples can be uncertain since it is difficult to avoid contamination of cell samples between the cervix and the vagina. Herein, cell samples were carefully collected by independently scraping the cervix and vagina, after which the HPV types were determined. HPV tissue tropism was determined by considering what HPV types were positive at only one of the sites (the cervix or the vagina) as the viruses that preferentially infected that site. This method revealed that all LR types were only identified in vaginal samples, whereas 87% of HR types were identified in cervical sites. Thus, LR types may preferentially infect the vagina, whereas HR types infect the cervix. These findings suggest that preferential tissue tropism of certain HPV types is a probable factor for malignant progression.

Comparison of Aptima and hybrid capture-2 HPV tests and Pap test in the referral population in Japan.

The Aptima human papillomavirus (HPV) test (APTIMA) detects E6-E7 mRNA in abnormal cells in the uterine cervix. To investigate the accuracy of APTIMA for cervical cancer screening in Japan, 423 subjects, mostly referrals with abnormal cytology or being followed up for cervical intraepithelial neoplasia (CIN)1, were screened using two HPV tests, hybrid capture 2 (HC2) and APTIMA, and by the Pap test. Colposcopy was conducted in all subjects with a positive result in either test type. HPV genotyping was performed by Genosearch-31. A result of atypical squamous cells-undetermined significance (ASC-US) or worse on the HC2 test (ASC-US-HC2), and low-grade squamous intraepithelial lesion (LSIL) or worse (LSIL+) on the Pap test, was regarded as positive. APTIMA (97.5%) was more sensitive than LSIL+ (85.1%) for detecting CIN2 or worse (CIN2+) (McNemar test; p = .0003), and more sensitive (98.6%) than ASC-US-HC2 (92.7%) for detecting CIN3+. APTIMA and HC2 had similar sensitivities. HPV genotyping revealed that CIN2/3 with high-risk HPV (HR-HPV) was overlooked in five cases by ASC-US-HC2, and in four cases by HC2, while no such lesions were missed by APTIMA. Thus, APTIMA might be superior to HC2 for primary HPV screening in Japan. One cancer case positive for HPV67 (potentially high risk, [pHR]) was overlooked by Pap test and both HPV tests, suggesting a need for a new HPV test able to detect pHR-HPV types.

The prevalence of VAIN, CIN, and related HPV genotypes in Japanese women with abnormal cytology.

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.

Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential.

Koilocytes are considered a common cytopathological effect in patients with human papillomavirus (HPV) infection. Thus, we aimed to elucidate whether koilocytes are common to all HPV infections. Liquid-based cytology samples from 651 patients with abnormal Papanicolaou (Pap) test results were used to analyze the presence of koilocytes and HPV genotype. HPV genotype was determined in complete liquid cytology samples and microdissected cell samples from Pap smear slides using the uniplex E6/E7 polymerase chain reaction method, which can detect 39 mucosal HPV genotypes. Koilocytes were found in 29.3% (191) of all patients. Logistical regression analysis of diverse HPV genotypes revealed that infections with low-risk HPV types (HPV-6b, HPV-40, HPV-42, HPV-61, HPV-74, HPV-89, and HPV-90), probably high-risk HPV types (HPV-53 and HPV-66), and high-risk types (HPV-39 and HPV-56) were significantly associated with the presence of koilocytes. However, HPV-16, HPV-18, and HPV-52, which have higher oncogenic potential, were not found to be associated with koilocytes. These results were confirmed by HPV genotyping using microdissected koilocytes in 27 patients.Most common high-risk types belonging to α-9 and α-7 genotypes appear to rarely induce koilocytic changes. Therefore, koilocytes may provide additional useful information for predicting the risk of progression to high-grade lesions.

Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells.

Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (-) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.

Uniplex E6/E7 PCR method detecting E6 or E7 genes in 39 human papillomavirus types.

We have developed a new human papillomavirus (HPV) assay using the uniplex E6/E7 polymerase chain reaction (PCR) method, which is able to detect E6 and E7 genes in 39 HPV types. We validated the assay for sensitivity and specificity using cloned HPV DNA and clinical samples. A comparative study using Genosearch-31 (GS-31) to determine HPV genotypes in clinical samples was also performed. E6 or E7 genes, measured by uniplex E6/E7 PCR, were detectable in 15 low-risk (HPV-6, -11, -40, -42, -44, -54, -55, -61, -62, -71, -74, -81, -84, -89, -90), 11 intermediate-risk (HPV-26, -30, -34, -53, -66, -67, -69, -70, -73, -82, -85), and 13 high-risk (HR) HPV types. The detection limit of this assay was 100 copies in all 39 HPV types and no cross-reactivity was observed with any type. This assay detected HPV in all 226 cervical cell samples, including 222 high-grade squamous intraepithelial lesions (HSIL) and 4 squamous cell carcinoma (SCC) cases, whereas GS-31 identified HPV in 99.6% (225/226) of the same samples. All SCC and 41.0% (90/222) of HSIL cases were infected with a single HPV type, while the remaining 59% of HSIL cases involved multiple HPV types. It was noted that high-risk and probably high-risk HPV types (HPV-66, -70 and -82) were identified, but no low-risk types were identified as a single-type infection in these HSIL and SCC cases. The uniplex E6/E7 PCR assay has high sensitivity, and can be useful tool in epidemiological studies or clinical follow-ups after surgery.

Comparison of the digene hybrid capture 2 and Roche cobas 4800 HPV tests for detection of CIN2+ in a referral population in Japan.

To examine validity of the hybrid capture-2 and cobas 4800 HPV tests, 396 women including 188 women visiting for cancer screening, and 208 referral cases were examined with both HPV tests and the liquid-based cervical Pap test. Concordant results between the HPV assays were observed in 333 cases (coincident rates; 84.1%, kappa value; 0.682). The sensitivity for CIN2+ was 98.6% (69/70) and 82.9% (58/70) for HC2 and cobas 4800 (McNemar's test; P = 0.0026). The sensitivity for CIN3+ was 97.2% (35/36) and 83.3% (30/36) (Not significant, P = 0.0736). The specificities for CIN2+ or CIN3+ did not differ between the tests. The HPV16, 52, 18, 31, and 58 were the most common types in CIN2+ cases. Reasonable sensitivity for HPV52, and cross-hybridization with some probable high-risk HPV type such as HPV82 explain the higher sensitivity of HC2 than cobas 4800 in detection of CIN2+ in a referral population in Japan.

Association between intimate partner violence during pregnancy and maternal pregnancy complications among recently delivered women in Bangladesh.

Intimate partner violence (IPV), an actual or threatened physical, sexual, or psychological abuse by a current or former partner or spouse, is a common global public health issue. Understanding both the prevalence of IPV during pregnancy and its potential impact on the health of pregnant women is important for the development and implementation of interventions to prevent maternal morbidity and mortality. The purpose of this study was to explore the association between maternal experiences of IPV during pregnancy and pregnancy complications. A health-facility-based cross-sectional study was conducted from July 2015 to April 2016 among 400 randomly selected women who were admitted to the postnatal wards of Rajshahi Medical College Hospital for delivery. Data were collected through face-to-face interviews using a structured questionnaire. Multivariable logistic regressions were performed to assess relationships between variables of interest after controlling for potential confounders. Results indicated that 39.0% of women reported physical IPV and 26.3% of women reported sexual IPV during pregnancy. Additionally, 69.5% of women experienced medical complications (MCs); of this group, 44.3% experienced obstetric complications (OCs) and 79.3% experienced any pregnancy complication (AC) during their last pregnancy. The experience of physical IPV during pregnancy was significantly associated with the experience of MCs (adjusted odds ratio (AOR): 2.05, 95% confidence interval (CI): 1.15-4.01), OCs (AOR: 4.23, 95% CI: 2.01-7.12) and AC (AOR: 5.26, 95% CI: 2.98-10.52). Women who experienced sexual IPV during pregnancy were also at increased risk of suffering from any MC, any OC, and AC. Maternal experience of IPV during pregnancy is positively associated with pregnancy complications. Preventing IPV directed at pregnant women might reduce maternal morbidity and mortality in Bangladesh.

Population-based study for human papillomavirus (HPV) infection in young women in Japan: A multicenter study by the Japanese human papillomavirus disease education research survey group (J-HERS).

A multi-center study was conducted to examine 6,628 eligible Japanese women aged from 16 to 50 years for uterine cervical abnormality and HPV infection with a liquid based-cytology test and a novel HPV test using the PCR-SSOP-Luminex(®) method identifying 31 HPV genotypes. In 3,047 normal subjects, the overall prevalence across all HPV types was 25%, while that of the common 13 high-risk (Common-13HR) types (HPV-16, 18. 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) was 17%, and that of the definite high-risk (Definite-HR) types (HPV-16, 18. 31, 33, 35, 45, 52, and 58) was 12%. For Definite-HR, HPV-52, 16, and 58 were the most common, HPV-31 was relatively common, and HPV-18 was less common, while HPV-33, 35, and 45 were rare. Seven Definite-HR excluding HPV-45 and seven Possible-HR (HPV-39, 51, 56, 66, 68, 70, and 82) HPV types were identified as a single type infection in patients with high-grade squamous intraepithelial lesion (HSIL) or worse. The Common-13HR types were detected in 89% of subjects with HSIL, whereas either Definite-HR or Possible-HR types were detected in 95% of HSIL. These 1420 HPV types appear to be involved with HSIL or worse in Japan. The prevalences of multiple-type HPV infections were identified in roughly half of HPV-positive subjects, and decreased significantly with age in normal population and abnormal cytology groups, although the prevalences of single-type infections increased with age in the latter group. Most HPV infections are cleared for some years, while a certain HR-HPV type persists to induce HSIL.

Prevalence of human papillomavirus infection in the oropharynx and urine among sexually active men: a comparative study of infection by papillomavirus and other organisms, including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance due to the increasing incidence of human papillomavirus (HPV)-associated OSCC. However, the mode of HPV transmission to the oral cavity is poorly understood, and little is known about the epidemiology of oral HPV infection in men. The prevalence rates of HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. were compared in the oropharynx (oral cavity) and urine of male Japanese patients attending a sexually transmitted disease clinic. METHODS: The study population consisted of 213 men aged 16 - 70 years old (mean: 34.4 years old). Oropharyngeal gargles and urine were collected, and sedimented cells were preserved in liquid-based cytology solution. After DNA extraction, ß-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was determined by HPV GenoArray test. RESULTS: ß-Globin was positive in 100% and 97.7% of oral and urine samples, respectively. HPV detection rates were 18.8% and 22.1% in oral and urine samples, respectively, suggesting that the prevalence of HPV infection in the oral cavity was similar to that in the urinary tract. N. gonorrhoeae was more prevalent in oral (15.6%) than urine samples (9.1%), whereas C. trachomatis was detected more frequently in urine (15.9%) than oral samples (4.2%). The detection rates of M. genitalium, M. hominis, and Ureaplasma spp. were 5.2%, 10.3%, and 16.0% in oral samples, and 7.7%, 6.3%, and 19.2% in urine, respectively. There were no significant differences in the detection rates of Mycoplasma spp. and Ureaplasma spp. between anatomical locations. The distribution of HPV types were similar in oral and urine samples, and HPV16 was the most common type. The majority of men with HPV infection in both the oral cavity and urine had concordant oral and urinary HPV infection. The presence of urinary HPV infection was an independent risk factor of oral HPV infection, with an odds ratio of 3.39 (95% CI: 1.49 - 7.71), whereas oral gonococcal infection was inversely correlated with oral HPV infection (odds ratio: 0.096; 95% CI: 0.01 - 0.77). CONCLUSIONS: Oral HPV infection commonly occurs in sexually active men, and is significantly correlated with urinary HPV infection.

Human papillomavirus infection and pathogenesis in urothelial cells: a mini-review.

Several recent studies described that high-risk human papillomavirus (HPV) infection could have a potential role in the development of malignancies other than cervical cancer, such as laryngeal carcinoma, penile carcinoma, and anal carcinoma. However, the etiological role of HPV infection in the pathogenesis of urinary tract has not been clarified. Many epidemiological studies demonstrated that HPV infections frequently occur in the external genitalia through sexual contact; however, it was reported that HPV infection could also occur in the urinary tract, including the urethra and urinary bladder. Some morphological changes of cells associated with HPV infection and mild atypical cells, suspected to be intraneoplasia, were seen in HPV-positive samples obtained from the urinary tract. Some clinical studies and meta-analysis have indicated that HPV infection is likely to have a certain etiological correlation with the development of bladder carcinoma, although its prevalence may vary according to HPV type, study population, region, histological type, detection methods, and other variables. According to the results of previous studies, the prevalence of HPV greatly widely varies in cases of bladder carcinoma. Further research by case-control or large-scales studies is thus required to reach a more definite conclusion.

Quantification of HPV16 E7 Oncoproteins in Urine Specimens from Women with Cervical Intraepithelial Neoplasia.

We present the validity of using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for quantifying high-risk human papillomavirus (HPV) 16 E7 oncoproteins in urine specimens as a noninvasive method of analyzing the oncogenic activity of HPV. Some reports claim that the oncogenic activity of HPV is a more relevant clinical indicator than the presence of HPV DNA for estimating malignant potential. In the present study, urine containing HPV16 and related types were selected by uniplex E6/E7 polymerase chain reaction and classified according to the pathologic diagnosis of cervical intraepithelial neoplasia (CIN) in cervical biopsy specimens. Our ultrasensitive ELISA was able to detect attomole levels of HPV16 E7 oncoproteins, and it detected HPV16-positive SiHa cells at >500 cells/mL without detecting HPV18-positive cells. Our ELISA results showed E7 oncoproteins in 80% (4/5) of urine specimens from women with HPV16-positive CIN1, 71% (5/7) of urine specimens from CIN2 patients, and 38% (3/8) of urine specimens from CIN3 patients. Some urine specimens with undetectable E7 oncoproteins were thought to be negative for live HPV 16-positive cells or in an inactivated state of infection. These results provide the basis for assessing oncogenic activity by quantifying E7 oncoproteins in patient urine.

E6 and E7 variants of human papillomavirus-16 and -52 in Japan, the Philippines, and Vietnam.

Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV-16), which is most common worldwide, and HPV-52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV-16 or HPV-52. Samples were amplified further for their E6/E7 genes using type-specific primers and analyzed genetically. Seventy-nine HPV-16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African-2. The prevalences of HPV-16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV-52 E6/E7 genes analyzed successfully were grouped into four lineages, A-D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV-16 and HPV-52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV-16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV-16 and HPV-52 E6/E7 genes can be a useful molecular-epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia.

Risk factors of heavy uterine bleeding in patients with endometriosis and adenomyosis treated with dienogest.

OBJECTIVE: Dienogest (DNG), a fourth-generation progestin, reduces pain associated with endometriosis and uterine adenomyosis; however, it is associated with irregular uterine bleeding that can cause anemia and poor quality of life. We investigated risk factors for heavy bleeding following DNG administration. MATERIALS AND METHODS: We retrospectively investigated patients who received DNG for risk factors of heavy uterine bleeding, including clinical diagnosis, use of pretreatment gonadotropin-releasing hormone agonist, smoking, cancer antigen 125, and blood hormone levels. We additionally assessed the uterine area in patients with uterine adenomyosis, the major axis of the uterine body, the major axis of myometrial thickness, the site of tumor development, and the site of myoma development in patients with uterine fibroids. RESULTS: Eighty Japanese patients were administered DNG. The median age was 41 (range: 24-51) years. The odds ratio (OR) for moderate-to-severe bleeding according to clinical diagnosis were 0.33 (P = 0.011) for endometrioma and 9.00 (P = 0.049) for uterine adenomyosis. Receiver operating characteristic curve analysis of the uterine area associated with uterine adenomyosis showed an area under the curve (AUC) of 0.909 between those with major and minor bleeding, with an optimal cut-off value of 7388.2 mm2. The uterine body major axis had an AUC of 0.946, with an optimal cut-off value of 78.3 mm. The major axis of myometrial thickness had an AUC of 0.855, with an optimal cut-off value of 46.8 mm. CONCLUSION: Patients with endometrioma treated with DNG were less likely to experience heavy uterine bleeding. Uterine bleeding in patients with uterine adenomyosis and adenomyosis associated with uterine fibroids should be closely monitored while administering DNG.

Chemical Peeling Therapy Using Phenol for the Cervico-Vaginal Intraepithelial Neoplasia.

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervical and vaginal intraepithelial neoplasia (CIN and VaIN, respectively), with the goal of circumventing obstetric complications associated with surgical treatment and to determine the factors associated with treatment resistance. Methods: A total of 483 eligible women diagnosed with CIN, VaIN, or both, participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks or by colposcopy. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Our preliminary analysis compared the recurrence and persistence rates between 294 individuals who received phenol-based chemical peeling therapy and 189 untreated patients. Results: At 2 years following diagnosis, persistent disease was observed in 18%, 60%, and 88% of untreated patients with CIN1-3, respectively, and <2% of patients with CIN who received phenol-based chemical peeling therapy. Among 483 participants, 10 immune-suppressed patients required multiple treatments to achieve disease clearance, and 7 were diagnosed with cervical cancer. Of the 466 participants, except those with cancer or immune suppression, the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 42 (average: 9.2 sessions). In total, 43 participants (9.2%) underwent surgical treatment. Six patients (1.3%) experienced recurrence of CIN2 or worse, suggesting that treatment failed in 46 patients (9.9%). No obstetrical complications were noted among the 98 pregnancies following this therapy. Factors associated with resistance to this therapy include immune suppression, ages 35-39 years, higher-grade lesions, and multiple HPV-type infections. Conclusions: Phenol-based therapy is safe and effective for CINs and VaINs. Women aged < 35 years and with persistent CIN1 or CIN2 with a single HPV-type infection are suitable candidates for phenol-based chemical peeling therapy. However, this therapy requires multiple lengthy sessions.

[Associations between Maternal Postpartum Depression and Psychosocial Factors Including Marital Relationship and Social Support].

OBJECTIVES: We aimed to investigate the psychosocial factors for postpartum depression as indicated by a high score of the Edinburgh Postnatal Depression Scale (EPDS), including marital relationship and social support. Relevant factors for antenatal depression were also analyzed. METHODS: Thirty-five wife-and-husband pairs who visited University Hospital A for the wife's antenatal health check-up participated in a questionnaire survey using the Japanese version of the EPDS. Social support from the wife's husband, kins, and others including friends at the third trimester of pregnancy and 1 month after birth was assessed. The Marital Love Scale (MLS) was also used, and two marital relationship questions were asked regarding the husband's and wife's considerate actions toward each other during pregnancy. Binary logistic regression analysis was conducted to determine adjusted associations between higher EPDS scores (≥5 for postpartum depression and ≥7 for antenatal depression) and indicators for social support and marital relationships. RESULTS: The most relevant factor for higher postpartum EPDS scores was a higher antenatal EPDS score, followed by the couple's poor communication skills (the wife did not feel any appreciation from her husband) during pregnancy and no support from the wife's husband during the postpartum period. The wife's poor marital communication skills and the husband's low MLS scores during pregnancy were associated (borderline significance) with the wife's higher antenatal EPDS scores. CONCLUSIONS: A good marital relationship before birth and support by the husband after birth may be important for preventing postpartum depression.

Liquid-based urine cytology as a tool for detection of human papillomavirus, Mycoplasma spp., and Ureaplasma spp. in men.

Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The ß-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis.

Novel polymerase chain reaction method for detecting cutaneous human papillomavirus DNA.

There is no simple test to identify the human papillomavirus (HPV) genotypes that cause cutaneous warts. A new polymerase chain reaction (PCR) method, called SK-PCR, was developed for this purpose. This PCR amplifies 210-238 base pairs of L1 DNA of 17 HPV types (HPV-1a, -2a, -3, -4, -7, -10, -27, -28, -29, -40, -57, -60, -63, -65, -77, -91, and -94), which are thought to cause various cutaneous warts, including common, flat, butcher's, punctate, and pigmented warts. The method is novel because the location of these primers is completely different from that of any previous PCR method for HPV. The target sequences are specific to alpha-, gamma-, and mu-papillomaviruses (PVs), but not to beta-PVs. Furthermore, direct sequencing and restriction fragment length polymorphism (RFLP) were used to determine the HPV genotypes. Fifty of samples of plantar warts were examined, and HPV-27 was identified in 22 warts, HPV-57 in 15 warts, and HPV-2a in 9 warts. These PVs, which are alpha species 4, were the most common. HPV-4 and -65 (gamma-PVs) and HPV-1a and -63 (mu-PVs) were detected in one case each. A single HPV type was identified in all of these warts. This method appears to be useful for genotyping the HPVs causing skin warts, and for distinguishing between HPV-induced warts and warty lesions unrelated to HPV infection.