Multiple Human Papillomavirus Infections Research Articles

Abstract A018: A case of Buschke-Löwenstein tumor with superimposed infection and associated urothelial carcinoma

Abstract The Giant Condyloma Acuminata (GCA), the Buschke-Löwenstein tumor, is a rare and challenging pathology with a less than 0.1% prevalence. This disease is often considered a transitional phase between condyloma acuminatum and squamous cell carcinoma, potentially representing a variant of verrucous carcinoma. Despite its initially benign histological presentation, GCA can evolve into expansive papillomatous proliferations that deeply invade underlying tissues. Studies indicate that GCA may transform into invasive squamous cell carcinoma in 8.5-23.8% of cases. The strong correlation between GCA and human papillomavirus (HPV) infections, particularly subtypes 6 and 11, underscores the role of viral factors in developing this condition. The presented case involves a 57-year-old male with pre-existing medical conditions, including hypertension and diabetes mellitus, who sought emergency care due to escalating suprapubic and penile discomfort. A biopsy of the genital warts identified condyloma acuminatum with an overlying bacterial infection of Proteus mirabilis. Concurrently, pathology identified anogenital squamous cell carcinoma. Notably, the patient had no associated sexually transmitted infections and no prior immunocompromised status. Imaging studies revealed a multilobulated soft tissue mass in the pelvis with prostatic invasion and enlarged lymph nodes. Further investigations, including a transurethral resection of bladder tumor (TURBT), revealed multiple tumor deposits in the bladder, penile lesion, and suprapubic papule. Pathological examinations indicated non-invasive and invasive papillary urothelial carcinoma as well as invasive squamous cell carcinoma in different locations. The tumor was staged as pathologic IIIB T2N3M0, and a collaborative decision between Urology and Oncology teams led to the initiation of neoadjuvant chemotherapy with TIP (cisplatin, ifosfamide, and paclitaxel). The patient underwent the initial chemotherapy cycle with subsequent cycles scheduled every three weeks. Management options for GCA include radiotherapy, cryosurgery, CO2 laser surgery, systemic chemotherapy, and radical surgical excision. While radiotherapy has shown successful outcomes, concerns about anaplastic transformations and post-treatment condylomas make its utilization contentious. The absence of unequivocal guidelines for radiotherapy dosage and fractionation has led to considerations of alternative modalities, but the primary approach remains radical surgical excision. The risk of recurrence remains high due to potential tumor cell spillage during surgery. In conclusion, this case report highlights an advanced manifestation of the Buschke-Löwenstein tumor coexisting with multiple HPV infections. The complexity of GCA and the lack of consensus on optimal therapeutic strategies emphasize the need for timely diagnosis and intervention to ensure favorable prognoses. Various treatment paradigms exist in medical literature, but their efficacy varies, reflecting the ongoing challenges in managing this rare and clinically intricate condition. Citation Format: Aliya M. Khan, Sophia Navajas, Mehmet Hepgur, Samuel A. Kareff. A case of Buschke-Löwenstein tumor with superimposed infection and associated urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A018.

HPV genotyping in clinical samples using long-read single-molecule real-time sequencing.

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high-risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real-time sequencing (SMRT) and evaluated its performance against MY09-11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09-11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR-HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR-HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype.

Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18–45 years

ABSTRACT To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18–45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

The role of multiple high-risk human papillomavirus infection on the persistence recurrence of high-grade cervical lesions after standard treatment: A systematic review and a meta-analysis.

The role of multiple high-risk human papillomavirus (HR-HPV) infections on the occurrence of persistence/recurrence of high-grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated. A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022. Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed-up and included in the meta-analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3-23.5) in multiple and 14.3 (95% CI: 10.1-19.2) in single HR-HPV infections detected shortly before or at surgery. The pooled rate of multiple HR-HPV infections was 25% (95% CI: 20.4-30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08-1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR-HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR-HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18-1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow-up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17-2.37, heterogeneity = 37%). Multiple HR-HPVs infection detected during follow-up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68-1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low-moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23-2 for low-moderate risk of bias and OR: 1.06, 95% CI: 0.65-1.75 for high risk of bias; p-value for subgroup differences = 0.17). Multiple HR-HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow-up plan.

Feasibility and Acceptability of Self-sampling for Human Papillomavirus DNA Testing Among Asymptomatic Women in Rural Delta State, Nigeria

Background: Self-sampling and human papillomavirus (HPV) DNA testing can be vital tools in cervical cancer screening for hard-to-reach women with limited access to health care in sub-Saharan Africa. This study explored the feasibility and acceptability of self-sampling for HPV testing among asymptomatic women in Orhuwhorun community in Delta State. Methods: This was a cross-sectional study of 230 women aged between 30 - 65years, enrolled by a multi-stage sampling method. Recruited women were asked to provide self-collected vaginal samples between May and June, 2021. HPV detection and genotyping was done using 21 HPV Geno-Array Diagnostic kit. Participants were asked to complete questionnaires after self-sampling to point out their experiences and acceptability of HPV self-sampling. Results: An excellent feasibility of self-sampling (95.2%) was observed. The acceptability rate of self-sampling was 93.0%, and 99.6% (229/230) of the participants were confident that they used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 21.1% (48/228) of the samples were positive for HPV, including 12.3% (28/228) with high-risk HPV types,2.6% (6/228) with probable high risk HPV types and 1.8% (4/228)with low-risk HPV types. Multiple HPV infection occurred in 10 cases (4.4%). Conclusion: This study indicates that self-sampling is a feasible and acceptable approach for cervical cancer screening among women in rural Delta State. Thus, the government should consider self-sampling as a valuable strategy in implementing national cancer screening programme.

Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type–Specific Attribution

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

Characteristics of human papillomavirus prevalence and infection patterns among women aged 25–64 according to age groups and cytology results in Ordos City, China

BackgroundThe assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population.MethodsThe analysis included a total of 26,692 women aged 25–64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated.ResultsAmong 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35–64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (Ptrend < 0.001).ConclusionIn conclusion, the epidemiology of HPV genotypes partly reflects the effectiveness of regional cervical cancer prevention and control efforts in the past. These findings can inform future initiatives concerning HPV vaccination and screening in the region.

Prevalence of Multiple High Risk Human Papilloma Virus (HR-HPV) Infections in Cervical Cancer Screening in Lazio Region, Italy.

It has been well established that human papilloma virus (HPV) is the major cause of cervical pre-cancerous lesions and cervical cancer. Extended HPV genotyping has pointed out that co-infections with multiple high-risk (HR)-HPV genotypes not only is possible and quite frequent, but also has different prognoses. The purpose of this study was to evaluate the prevalence of co-infections in women tested for HR-HPV in the national cervical cancer screening program of Lazio (Italy). From June 1st to November 30th 2022, we analyzed 30,445 samples of women aged between 30 and 64 years, using the Anyplex TM II HPV HR Detection test by Seegene (Arrow), which identifies 14 HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68. The data were analyzed using the SG STATS platform. In total, 4,244 (13.94%) were positive: 3,290 (77.52%) showed a single genotype infection and 954 (22.48%) an infection with 2 to 5 different genotypes. In 721 (75.60%) cases, two different genotypes were detected, in 191 (20.00%) there were three genotypes, in 41 (4.30%) cases there were four genotypes and in only one case (0.10%) five different genotypes were detected. HPV 16 (262 cases of co-infections) was associated in 27 cases with HPV 31 genotype, in 25 cases with HPV 68 and in 18 cases with HPV 58. HPV 16 was the most frequent genotype detected in co-infections. Immunity status, vaccination, lifestyle, and other possible risk factors, such as the combination of the HR-HPV genotype multiple infections, may influence the development and progression of the disease.

Characteristic of persistent human papillomavirus infection in women worldwide: a meta-analysis.

We aimed to estimate the genotype distribution of persistent human papillomavirus (HPV) infection in females worldwide, and provided a scientific basis for the prevention strategies of cervical cancer (CC) and the development of HPV vaccines. Both English and Chinese databases were researched from the inception to July 2023. The pooled persistent HPV infection prevalence was calculated using a random effects model. The subgroup analysis was performed to explore the heterogeneity. Publication bias was evaluated using funnel plot, Egger's and Begg's test. Twenty-eight studies with 27,335 participants were included. The pooled prevalence of persistent HPV infection was 29.37% (95% CI [24.05%∼35.31%]), and the genotypes with the persistent infection prevalence were HPV16 (35.01%), HPV52 (28.19%), HPV58 (27.06%), HPV18 (25.99%), HPV33 (24.37%), HPV31 (23.35%), HPV59 (21.87%), HPV39 (19.54%), HPV68 (16.61%) and HPV45 (15.05%). The prevalence of multiple and single HPV persistent infection were 48.66% and 36.71%, respectively; the prevalence of persistent HPV infection in different age groups (<30, 30∼39, 40∼49, >50) were 29.83%, 28.39%, 22.24% and 30.22%, respectively. The follow-up time was significantly associated with heterogeneity by subgroup analysis (P<0.05), and the prevalence of persistent infection decreased with longer follow-up time. Multiple infections were more likely to occur persistent HPV infection than single infection. In addition to HPV vaccination, we should emphasize the follow-up management for women under 30 and over 50 years old, those with high-risk HPV infection (HPV59, 39, 68) and multiple infections.

Associations of multi-human papillomavirus infections with expression of p16 in a cohort of women who underwent colposcopy: a retrospective study of 5165 patients.

Investigate HPV types in cervical specimens, their correlation with p16 expression in lesions, and diagnostic value for cervical lesions. Enhance clinical diagnosis reliability. Retrospective cross-sectional study at Fujian Maternity and Child Health Hospital's Cervical Disease Center (Jun 2019-Dec 2021). Patients with abnormal cervical screening underwent colposcopy and conization. Pathological diagnosis based on colposcopy, cervical biopsy, ECC, and conization. Analyzed HPV genotyping (18 HR-HPV, 5 LR-HPV) and p16 expression correlation. Statistical analysis used R software. he expression of p16 is significantly associated with the infection of high-risk HPV types, such as 16, 33, 52, and 58, with an increased risk of 1.4 times or higher (OR=1.91, 3.14, 1.40, and 1.78, respectively). The risk of p16 expression increased 4-fold for multiple high-risk HPV types [adjusted OR (95% CI) = 4 (2.92~5.5), P-value <0.001]. Compared to the p16(-) group, the p16(+) group had a higher association with cervical lesions worse than HSIL (High-grade Squamous Intraepithelial Lesions).In the group with multiple Human Papillomavirus Infections with types 16, 33, 52, and 58, the risk of cervical lesions worse than HSIL increased by up to 660-fold compared to the negative group (adjusted OR=660.62, 95% CI: 91.39~4775.53, P<0.001), indicating that this combination of HPV types posed the greatest risk for cervical lesions above HSIL. p16 plays a crucial role in cervical lesion progression, linked to high-risk HPV. Combining p16 with HPV screening improves cervical cancer detection. Studying multiple HPV infections will enhance prevention and management.

Single and Multiple High-Risk Human Papillomavirus Infections in Histopathologically Confirmed Cervical Squamous Lesions: Incidences, Distribution, and Associated Detection Rates for Precancerous and Cancerous Lesions

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022. Among 49,299 cases with hrHPV genotyping and histologic diagnosis, 24,361 cases were diagnosed as cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma. Among women with cervical squamous lesions, 86.5% (21,070/24,361) had hrHPV infections, and concomitant multiple hrHPV infections accounted for 24.7% of hrHPV-positive cases (5210/21,070). The hrHPV-positive rates in these cervical squamous lesions increased progressively with disease severity; however, the percentages of concomitant multiple hrHPV infection rates among hrHPV-positive cases decreased significantly with increasing degree of squamous abnormalities. There was no increased detection rate of CIN3+ (CIN3 and squamous cell carcinoma) in cases with concomitant 2 or 3 hrHPV genotype infections when compared with those with corresponding single hrHPV infections. Conversely, some combinations of multiple hrHPV infections demonstrated a decrease in the detection rates of CIN3+ lesions. In this large cohort, our results demonstrated that multiple hrHPV infections do not carry an increased risk for developing CIN3+ lesions when compared to the corresponding single-genotype infection. The reduced risk of CIN3+ in women infected with some combinations of hrHPV genotypes compared to those with single-genotype infections supports the concept of intergenotypic competition of hrHPV genotypes in cervical squamous lesions.

Prevalence of Human Papillomavirus (HPV) Genotypes among Women During 2015-2020 in Mashhad, Iran.

Cervical cancer is the fourth most common cancer in women, and human papillomavirus (HPV) is the leading cause of cervical cancer. Cervical cancer screening and HPV vaccination are important in the incidence of cervical cancer. This study was performed on Liquid Base Cytology (LBC) samples of 1214 women in Mashhad who were referred for cervical cancer screening in 2015-2020. Samples were examined by Single-Step PCR and Reverse Line Blot for HPV genotyping. 386 women (31.8%) were HPV PCR positive. HPV genotyping of 277 samples showed that HPV 31 (3%), 16 (2.5%), 51 (2.2%), 18 (2%), and 66 (1.8%) were the most prevalent high-risk HPV (hrHPV) genotypes. Among low-risk HPV (lrHPV) genotypes, HPV 6 (9.2%), 53 (4.7%), and 42 (2.8%) were the most common genotypes. The range of multiple infections varied between two to eight genotypes and the prevalence of multiple HPV infections (12.4%) was higher than single infections (10.4%). For women with single HPV infections, HPV 31 and 66 were equally the most common hrHPV genotypes, followed by HPV 16 and 39. In women with multiple HPV infections, HPV 31 was the most common hrHPV genotype, followed by HPV 51 and 16. For both the single and multiple HPV infections, HPV 6 was the most common lrHPV genotype, followed by HPV 53 and 42. In conclusion, due to the high prevalence of HPV single and multiple infections, the need for governmentally supported HPV vaccination and through cervical cancer screening should be emphasized to prevent cervical cancer.

Multiple infections containing the top five prevalent HPV genotypes and their impact on cervical lesions in Changzhou, China

ABSTRACT Human papillomavirus (HPV) infection is the primary cause of cervical cancer and its precursor lesions. The overall prevalence of HPV genotypes in Changzhou has previously been reported. However, the distribution of multiple HPV infections and their roles in cervical injury have less been investigated. We aimed to assess the prevalence of multiple HPV infections among the people in Changzhou. Furthermore, we analyzed whether multiple HPV infections comprising the top five prevalent HPVs were more associated with abnormalities in E6 and E7 (E6/E7) mRNA, liquid-based cytology, and cervical histopathology than a single infection. In the current study, HPV 16, 52, 58, 53, and 81 were the top five prevalent HPV types, both in single and multiple infections. Compared to a single infection, multiple infections containing HPV 16/52/58 were closely linked to positivity for E6/E7 mRNA. In addition to HPV 16, multiple infections containing the remaining top four HPVs conferred a significant advantage on atypical squamous cells of undermined significance or worse in comparison to a single infection. Furthermore, women with multiple infections containing the top five prevalent HPV types were more likely to develop cervical intraepithelial neoplasia grade II or worse than those with a single HPV infection. Our results demonstrate the superiority of multiple HPV infections containing the top five prevalent HPV types in cervical disease progression, which should be closely monitored. These findings are conducive for formulating regional preventive strategies for cervical cancer screening and vaccination in Changzhou.

Prevalence and Genetype Distribution of Human Papillomavirus in Women with Condyloma Acuminatum in Henan Province, Central China.

This study aims to analyze the distribution of human papillomavirus (HPV) genotypes and the associations of demographic characteristics with HPV infection among women with condyloma acuminatum (CA) in Henan Province of China. From January 2019 to October 2022, 702 women with CA were sampled for HPV subtypes and surveyed by questionnaire at Henan Provincial People's Hospital. The HPV genotype was tested by flow-through hybridization after polymerase chain reaction (PCR). The location of warts was mainly vulva. The age of the subjects was mainly distributed in the 20-29-year-old, followed by 30-39-year-old. The most common subtypes were HPV 6 (43.59%), 11 (24.93%), 16 (11.82%), 52 (7.83%), 58 (7.55%), 51 (7.26%), 61 (5.70%), 39 (5.56%), 18 (5.13%), and 54 (4.70%), our results also suggested that HPV 6 and 11 were the dominant genotypes in each age group. The infection of low-risk HPV (LR-HPV) (74.50%) and single HPV (47.01%) were the main categories. In terms of educational level, women with senior high school or above were inclined to infect single and pure-LR HPV. Unmarried status, sometimes or never condom use increased the chances of multiple, pure high-risk (HR) and mixed HPV infections. Women with multiple sex partners were more likely to cause multiple and mixed HPV infections. Our experimental data on the prevalence and subtype distribution of HPV in women with CA could provide valuable reference for preventing CA in Henan Province. The application of the nine-valent vaccine provides a broad prospect for female CA prevention.

The role of multiple high-risk human papillomavirus infections for cervical biopsies and findings in colposcopic procedures

The clinical outcome of high-risk HPV (hr-HPV) infection varies according to genotype(s). Patients may harbor either one single hr-HPV (s-HPV) or multiple HPV (m-HPV) genotypes. Recently, the relationship between m-HPV infections and high-grade dysplasia has been investigated, and controversial results have been obtained. Therefore, the clinical significance of m-HPV is not clear. This study aimed to evaluate which group is associated with higher grade dysplasia by analyzing colposcopic punch biopsies. A total of 690 patients who were scheduled for a diagnostic excisional procedure between April 2016 and January 2019 due to the detection of high-grade cervical intraepithelial neoplasia (CIN 2/3) in colposcopy were included. Patients who were not scheduled for colposcopic examination or cervical punch biopsy, or who were scheduled for an excisional procedure due to smear-biopsy incompatibility or persistent low-grade dysplasia were excluded. Patients with a negative HPV test and an unknown HPV genotype were also excluded. Among the patients scheduled for excision (n=404), 74.5% had a s-HPV and 25.5% had a m-HPV infection. The proportion of CIN 1, 2 and 3 per patient in the m-HPV group was significantly higher than the s-HPV group (p=0.017). When this analysis was made for the number of CIN 2+3 per patient in the s-HPV and m-HPV groups, it was 1.29 (389/301) and 1.36 (140/103), respectively, and no difference was found (p=0.491). Patients in the m-HPV group, who underwent more colposcopic cervical biopsies, had higher numbers of CIN lesions, regardless of age and cytology results.

Characterization of HPV subtypes in invasive cervical cancer in Botswana patients using a pan-pathogen microarray technology

Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.

Impact of HPV molecular testing with partial genotyping as a feasibility study in cervical cancer community screening program in South India.

Cervical cancer can be eradicated by 2030 by the implementation of a global strategy involving the vaccination of young girls against human papillomavirus (HPV), screening 70% of women in 30-69 years of age and treating 90% of the women with precancerous lesions. For a country with a large population like India, all the three strategies can be a challenge. There is a need for implementation of a high throughput technology that can be scalable. Cobas 4800, a multiplexed assay based on quantitative polymerase chain reaction technology, identifies HPV 16 and HPV 18 along with the concurrent detection of 12 pooled other high-risk HPV infections. This technology was used to test 10 375 women from the South Indian community for the first time as a feasibility program. Upon testing, high-risk HPV was found in 595 (5.73%) women. A total of 127 women (1.2%) were found to be infected with HPV 16, 36 women (0.34%) with HPV 18 and 382 women (3.68%) with the 12 pooled high-risk HPV and multiple mixed infections were found in 50 women (0.48%). It was observed that there was a high prevalence of high-risk HPV in younger women, 30-40 years of age and a second peak was observed at 46-50 years of age. The second peak had higher mixed infections in the 46-50 years of age and this association was statistically significant. We found that 24/50 (48%) of the multiple mixed high-risk HPV infections were in the age group 46-50 years. The current study is the first attempt from India, on a completely automated platform using Cobas 4800 HPV test in a community screening program. This study shows HPV 16 and HPV 18 infections, when differentiated, can be valuable for risk stratification in community screening program. Women in the perimenopausal age (46-50yrs) showed a higher prevalence of multiple mixed infections, signifying a higher risk.

The vaginal microbiota among the different status of human papillomavirus infection and bacterial vaginosis.

Although human papillomavirus (HPV) infection plays a decisive role in causing tumors, its infection is insufficient for independently promoting cancer development and other co-factors facilitate the carcinogenic process. The objective of this study was to demonstrate the association between vaginal microbiota and high-risk human papillomavirus (HR-HPV) infection in women with and without bacterial vaginosis (BV). The study included 1015 women aged 21-64 who participated in cervical cancer screening in two areas of China from 2018 to 2019. Women were collected cervical exfoliated cell specimens and reproductive tract secretions samples for HR-HPV, BV and microbial composition testing. From the non-BV& HPV- group (414 HPV-negative women without BV) to the non-BV& HPV+group (108 HPV-positive women without BV), to the BV& HPV-group (330 HPV-negative women with BV) and then to the BV& HPV+group (163 HPV positive-women with BV), microbial diversity increased. The relative abundance of 12 genera, including Gardnerella, Prevotella, and Sneathia increased, while Lactobacillus declined. Correlation networks of these genera and host characteristics were disrupted in the non-BV& HPV+group, and the network trended more disordered in the BV& HPV+group. Besides, multiple HPV infection, certain HPV genotype infection and cervical intraepithelial neoplasia (CIN) status were associated with some microbes and higher microbial diversity. HPV shifted the composition and diversity of vaginal microbiota, and BV further reinforced the trend. The relative abundance of 12 genera increased and 1 genus decreased on account of BV and HPV infection, and some genera including Lactobacillus, Prevotella, and Sneathia were associated with some specific HPV genotypes infection and CIN.

Higher clearance rates of multiple HPV infections may explain their lower risk of HSIL: A retrospective study in Wenzhou, China.

Persistent human papilloma virus (HPV) infection is known to be associated with cervical lesions.The chief object of the study is to investigate if the pathogenicity of multiple HPV infections is different from a single infection. Furthermore, we would like to corroborate the discrepancy with clearance rates.Between August 1, 2020, and September 31, 2021, 5089 women underwent a colposcopy-directed biopsy in our hospital. We divided the 2999 patients who met the criteria into multiple and single HPV infection groups. The HPV genotypes were identified using the flow cytometry fluorescence hybridization technology. Binary logistic regression and survival analysis were used to perform statistics.Among HPV-positiveindividuals, 34.78% (1043/2999) were positive for 2 or more HPV types. After adjusting for the main factors, compared with single infection, multiple infections were associated with a significantly decreased risk of high squamous intraepithelial lesions (HSIL) (odds ratio [OR]: 0.570; 95% confidence interval [CI]: 0.468-0.694). In the mean time, the clearance rates of multiple infections were significantly higher (OR: 2.240; 95%CI: 1.919-2.614). When analyzing specific types covered by the 9-valent HPV vaccine, consistency between the lower risk of HSIL and the higher clearance rate was found in the most groups.Compared with a single infection, multiple HPV infections have a lower risk of HSIL, which may be related to its higher clearance rate. It suggests that aggressive treatment of multiple HPV infections early in their detection may be beneficial.

Maternal human papillomavirus infection during pregnancy and preterm delivery, a mother-child cohort study in Norway and Sweden.

Human papillomavirus (HPV) infection is common in women of reproductive age. Infection and inflammation are leading causes for preterm delivery (PTD), but the role of HPV infection in PTD and prelabor rupture of membranes (PROM) is unclear. We aimed to explore whether HPV infection during pregnancy in general, and high-risk-HPV (HR-HPV) infection specifically, increased the risk of PTD, preterm prelabor rupture of membranes (PPROM), PROM at term, and/or chorioamnionitis. In pregnant women, who were participating in a prospective multicenter cohort study from a general population in Norway and Sweden (PreventADALL, ClinicalTrials.gov NCT02449850), HPV DNA was analyzed in available urine samples at mid-gestation (16-22 weeks) and at delivery, and in the placenta after delivery with Seegene Anyplex II HPV28 PCR assay. The risk of PTD, PPROM, PROM, and chorioamnionitis was analyzed using unadjusted and adjusted logistic regression analyses for any 28 HPV genotypes, including 12 HR-HPV genotypes, compared with HPV-negative women. Further, subgroups of HPV (low-risk/possibly HR-HPV, HR-HPV-non-16 and HR-HPV-16), persistence of HR-HPV from mid-gestation to delivery, HR-HPV-viral load, and presence of multiple HPV infections were analyzed for the obstetric outcomes. Samples for HPV analyses were available from 950 women with singleton pregnancies (mean age 32 years) at mid-gestation and in 753 also at delivery. At mid-gestation, 40% of women were positive for any HPV and 24% for HR-HPV. Of the 950 included women, 23 had PTD (2.4%), nine had PPROM (0.9%), and six had chorioamnionitis (0.6%). Of the term pregnancies, 25% involved PROM. The frequency of PTD was higher in HR-HPV-positive women (8/231, 3.5%) than in HPV-negative women (13/573, 2.3%) at mid-gestation, but the association was not statistically significant (odds ratio 1.55; 95% confidence interval 0.63-3.78). Neither any HPV nor subgroups of HPV at mid-gestation or delivery, nor persistence of HR-HPV was significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis. No HPV DNA was detected in placentas of women with PTD, PPROM or chorioamnionitis. HPV infection during pregnancy was not significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis among women from a general population with a low incidence of adverse obstetric outcomes.