High-risk Human Papillomavirus Incidence Research Articles

The distribution of hrHPV genotypes among cervical cancer cases diagnosed across Ghana: a cross-sectional study

BackgroundThe burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs.MethodsA descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05.ResultsA total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV.ConclusionWe affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.

Natural History of Oral HPV Infection among Indigenous South Australians.

This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection.

Advanced Nanomedicine for High-Risk HPV-Driven Head and Neck Cancer.

The incidence of high-risk Human Papillomavirus (HR-HPV)-driven head and neck squamous cell carcinoma (HNSCC) is on the rise globally. HR-HPV-driven HNSCC displays molecular and clinical characteristics distinct from HPV-uninvolved cases. Therapeutic strategies for HR-HPV-driven HNSCC are under investigation. HR-HPVs encode the oncogenes E6 and E7, which are essential in tumorigenesis. Meanwhile, involvement of E6 and E7 provides attractive targets for developing new therapeutic regimen. Here we will review some of the recent advancements observed in preclinical studies and clinical trials on HR-HPV-driven HNSCC, focusing on nanotechnology related methods. Materials science innovation leads to great improvement for cancer therapeutics including HNSCC. This article discusses HPV-E6 or -E7- based vaccines, based on plasmid, messenger RNA or peptide, at their current stage of development and testing as well as how nanoparticles can be designed to target and access cancer cells and activate certain immunology pathways besides serving as a delivery vehicle. Nanotechnology was also used for chemotherapy and photothermal treatment. Short interference RNA targeting E6/E7 showed some potential in animal models. Gene editing by CRISPR-CAS9 combined with other treatments has also been assessed. These advancements have the potential to improve the outcome in HR-HPV-driven HNSCC, however breakthroughs are still to be awaited with nanomedicine playing an important role.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/μL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/μL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Accuracy of high-risk HPV DNA PCR, p16(INK4a) immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal cancer

BackgroundThe incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.MethodsThe accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.ResultsNinety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.ConclusionsSingle hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.

A Comprehensive Discussion in Vaginal Cancer Based on Mechanisms, Treatments, Risk Factors and Prevention.

Vaginal cancer is a rare and uncommon disease that is rarely discussed. Although vaginal cancer traditionally occurs in older postmenopausal women, the incidence of high-risk human papillomavirus (HPV)-induced cancers is increasing in younger women. Cervical cancer cells contain high-risk human papillomavirus (HPV) E6 and E7 proteins and inhibiting HPV gene expression leads the cells to stop proliferating and enter senescence. As E6, and E7 protein promoted the carcinogenesis mechanism, and here not only regulate the cellular degradation of P53, and pRb but also enhances the cell proliferation along with E6 protein targets the p53 for breakdown and subsequently promote the apoptotic cell death, and DNA repair inhibition, that is indispensable to the continue the lifecycle of the HPV. As a synchronous or metachronous tumor, vaginal cancer is frequently found in combination with cervical cancer. It is uncertain what causes invasive female vaginal organ cancer. HPV type 16 is the most often isolated HPV type in female vaginal organ cancers. Due to cancer’s rarity, case studies have provided the majority of etiologic findings. Many findings demonstrate that ring pessaries, chronic vaginitis, sexual behavior, birth trauma, obesity, vaginal chemical exposure, and viruses are all risk factors. Because of insufficient understanding and disease findings, we are trying to find the disease’s mechanism with the available data. We also address different risk factors, therapy at various stages, diagnosis, and management of vaginal cancer in this review.

Possible Reactivation of Latent Anal Human Papillomavirus Associated with Markers of Immune Dysfunction in Gay and Bisexual Men.

It is unknown whether reactivation of human papillomavirus (HPV) after latency occurs in the anus. We measured incidence and predictors of incident anal HPV in sexually inactive gay and bisexual men (GBM) as a surrogate of HPV reactivation. The Study of the Prevention of Anal Cancer collected data on sexual behavior, anal cytology, HPV DNA, histology and HPV serology. HPV incidence during periods when zero sexual partners were reported in the last six months at both the current and previous annual visit ("no sexual activity") was analyzed by Cox regression using the Wei-Lin-Weissfeld method to determine univariable predictors. Of 617 men enrolled, 525 had results for ≥2 visits, of whom 58 (11%) had ≥ one period of "no sexual activity". During sexually inactive periods, there were 29 incident high risk HPV infections in 20 men, which occurred more commonly in older men (Ptrend = 0.010), HIV-positive men (HR = 3.12; 95% CI, 0.91-16.65), longer duration of HIV (Ptrend = 0.028), history of AIDS defining illness (P = 0.010), lower current (P = 0.010) and nadir CD4 count (P = 0.014). For 18 of 29 infections with available results, 12 men remained type-specific HRHPV L1 seronegative. None were consistently seropositive. A new diagnosis of HSIL occurred in only two men, caused by an HPV type other than the incident type. Our findings suggest that in sexually inactive GBM, anal HRHPV incidence is relatively common, and is associated with increasing age and immune dysfunction, a pattern consistent with HPV reactivation. Reactivation of anal HPV may occur.

Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors.

While head and neck squamous cell carcinomas (HNSCC) are marginally decreasing due to the reduction in exposure to the major risk factors, tobacco and alcohol, the incidence of high-risk human papillomavirus (HPV)-positive oropharynx squamous cell carcinomas (OPSCC), especially those in the tonsil and base of tongue subsites, are increasing. Patients with the latter are younger, display a longer overall survival, and show a lower recurrence rate after standard-of-care treatment than those with HPV-negative OPSCC. This may reflect an important role for immune surveillance and control during the natural history of the virally driven tumour development. Immune deviation through acquisition of immune-suppressive factors in the tumour microenvironment (TME) is discussed in relation to treatment response. Understanding how the different immune factors are integrated in the TME battleground offers opportunities for identifying prognostic biomarkers as well as novel therapeutic strategies. OPSCC generally receive surgery or radiotherapy for early-stage tumour treatment, but many patients present with locoregionally advanced disease requiring multimodality therapies which can involve considerable complications. This review focuses on the utilization of newly emerged immune checkpoint inhibitors (PD-1/PD-L1 pathway) for treatment of HNSCC, in particular HPV-positive OPSCC, since they could be less toxic and more efficacious. PD-1/PD-L1 expression in the TME has been extensively investigated as a biomarker of patient response but is yet to provide a really effective means for stratification of treatment. Extensive testing of combinations of therapeutic approaches by types and sequencing will fuel the next evolution of treatment for OPSCC.

Persistence and clearance of high-risk human papillomavirus and cervical dysplasia at 1year in women living with human immunodeficiency virus: a prospective cohort study.

Evaluate 1-year outcomes of cervical cancer screening and treatment using primary high-risk human papillomavirus (HPV) testing in women living with human immunodeficiency virus (HIV). Prospective cohort study. HIV treatment centre in Botswana. Women living with HIV. Participants underwent cervical cancer screening with high-risk HPV testing and triage evaluation at baseline and 1-year follow up. Excisional treatment was offered as indicated. Histopathology was the reference standard. Persistence, clearance and incidence of high-risk HPV infection; and persistence, progression, regression, cure and incidence of cervical dysplasia. Among 300 women screened at baseline, 237 attended follow up (79%). High-risk HPV positivity significantly decreased from 28% at baseline to 20% at 1year (P=0.02). High-risk HPV persistence was 46% and clearance was 54%; incidence was high at 9%. Prevalence of cervical intraepithelial neoplasia Grade 2 (CIN2) or higher was most common in participants with incident high-risk HPV (53%). CIN2 or higher was also common in those with persistent high-risk HPV (32%) and even in those who cleared high-risk HPV (30%). Of the high-risk HPV-positive participants at baseline with <CIN2, 40% progressed to CIN2 or higher at follow up. The high incidence of high-risk HPV and high-grade cervical dysplasia in women living with HIV after one round of high-risk HPV-based screening and treatment raises concern about the rate of progression of high-risk HPV infection to dysplasia. Persistent disease is common. Caution in spacing cervical cancer screening intervals using high-risk HPV testing in women living with HIV is warranted. High incidence and persistence of HPV and CIN2+ in women living with HIV 1year after screening and treatment.

Type-specific incidence, persistence and factors associated with human papillomavirus infection among female sex workers in Benin and Mali, West Africa

ObjectivesThis study in female sex workers (FSWs) aimed to: (1) estimate type-specific incidence and persistence of human papillomavirus (HPV) infection in Cotonou (Benin) and Bamako (Mali); and (2) identify the factors associated with type-specific incidence and persistence of high-risk HPV (HR-HPV) infection. MethodsA 1-year prospective cohort study on cervical cancer screening, and HPV and human immunodeficiency virus (HIV) infections was conducted among FSWs in Cotonou and Bamako from 2017 to 2019. Poisson regression models assessed factors associated with the incidence of HR-HPV infection, while log-binomial regression was performed to identify factors associated with the persistence of HR-HPV infection. Adjusted relative risks (ARR) and 95% confidence intervals (95% CI) were estimated. ResultsThe incidence of HR-HPV infection was 46.98 per 1000 women-months (predominant types HPV16, HPV35 and HPV59). Factors associated with the incidence of HR-HPV infection were age <20 years (ARR 15.10; 95% CI 3.29–69.19), age at sexual debut <18 years (ARR 6.92; 95% CI 1.97–24.27) and sex work duration ≤1 year (ARR 7.40; 95% CI 1.84–29.69). The persistence of HR-HPV infection at 12 months was 38.7% (most persistent types HPV59, HPV52 and HPV51). Persistence of HR-HPV infection was higher in women with chlamydia (P = 0.031), HIV infection (P < 0.001) and multiple-type HPV infections (P < 0.001). ConclusionFSWs in West Africa are at high risk of incident and persistent HR-HPV infection, suggesting an urgent need for cervical cancer screening in this population.

Prevalence and genotype distribution of HPV infection among 214,715 women from Southern China, 2012\u20132018: baseline measures prior to mass HPV vaccination

BackgroundThe epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination.MethodsA retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People’s Hospital for cervical screening during 2012–2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed.ResultsThe overall HPV prevalence was 18.71% (95% confidence interval [CI], 18.55–18.88%) among Southern China females. During 2012–2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07–22.20%) in 2012 to 18.75% (95% CI, 18.35–19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13–35.15%), 20.07% (95% CI, 19.70–20.44%) among women aged 21–30 years, 17.29% (95% CI, 17.01–17.57%) among women aged 31–40 years, 17.23% (95% CI, 16.95–17.51%) among women aged 41–50 years, 21.65% (95% CI, 21.11–22.20%) among women aged 51–60 years, and 25.95% (95% CI, 24.86–27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11–22.20%), − 16 (2.96%; 95% CI, 2.89–3.03%), and − 58 (2.51%; 95% CI, 2.44–2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80–1.92%) and − 6 (0.69%; 95% CI, 0.66–0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study.ConclusionsThis study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012–2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, − 16 and − 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.

Incidence, persistence and clearance of cervical human papillomavirus among women in Guangdong, China 2007–2018: A retrospective cohort study

BackgroundPrevious studies showed the incidence, persistence and clearance of cervical human papillomavirus (HPV) among women varies from regions. There is no study on dynamic changes of HPV infection among women in Guangdong. MethodsIt is a retrospective cohort study that included gynecological outpatients aged ≥15 years and retested for HPV within 24 months in Guangdong Women and Children Hospital to estimate HPV incidence, persistence and clearance. Outcomes were estimated through the proportion of HPV incidence, persistence and clearance in HPV-negative or HPV-positive women. Moreover, we examined HPV incidence, persistence and clearance among women who retested in four calendar periods: 0–6, 6–12, 12–18, 18–24 months after the first test. Results33,328 gynecological outpatients were included in our study. Incidence rates of any HPV, high-risk (HR) HPV and low-risk (LR) HPV were 10.58%, 8.68% and 4.83%. The most common incident HR HPV were HPV52 (2.69%), HPV16 (1.23%) and HPV58 (1.23%). Persistence rates of any HPV, HR HPV and LR HPV were 47.55%, 42.77% and 33.88%. HPV52 (42.33%), HPV58 (40.74%) and HPV68 (32.36%) were commonly found persistent types. And clearance rates of any HPV, HR HPV and LR HPV were 52.44%, 57.23% and 66.12%.The lowest clearance rates were observed for HPV52 (57.67%), HPV68 (67.64%) and HPV39 (68.56%). HPV incidence and persistence were higher among women aged 15–19 years and ≥55 years. HPV incidence and persistence were found higher among women who retested within 6 months than others in other periods. ConclusionsHPV52, 58, 68, and 39 were the more likely to cause incident and persistent infection, and less likely to be cleared among women in Guangdong. HPV incidence and persistent infection were higher among women aged both younger and older women compared to middle aged women. HPV retesting period may impact the detection of HPV incidence, persistence and clearance.

Incidence, Persistence, and Factors Associated With HPV Infection Among Male Adolescents With and Without Perinatally Acquired HIV Infection.

Infection with high-risk human papillomavirus (HR-HPV) has been shown to be more prevalent and persistent in female adolescents with HIV. However, data among male adolescents with perinatally acquired HIV (PHIV) are limited. We investigated the incidence and persistence of HR-HPV in anogenital compartments and associated factors among PHIV in comparison to HIV-uninfected (HU) male adolescents in Thailand. PHIV and HU males aged 12-24 years were enrolled. At baseline and 3 subsequent annual visits, specimens from the scrotum, penis, and anal area were obtained for HPV and other testing. From June 2013 to October 2017, 49 PHIV and 47 HU male adolescents with a median age of 18 (interquartile range 17-20) years were enrolled. PHIV had higher incidence of any HR-HPV infection than HU adolescents {33.05 [95% confidence interval (CI): 20.82 to 52.46] vs. 15.73 [95% CI: 8.18 to 30.22] per 100 person-years, P = 0.04}. The persistence of any HR-HPV genotypes (detected at ≥2 annual visits) was not different by group (PHIV 27% vs. HU 23%, P = 0.75). Having ≥3 sex partners in past 6 months (adjusted prevalence ratio 2.39, 95% CI: 1.14 to 5.05; P = 0.02) and co-infection with other sexually transmitted infections (syphilis, chlamydia, and/or gonorrhea) were associated with persistent HR-HPV infection (adjusted prevalence ratio 6.21, 95% CI: 2.87 to 13.41; P < 0.001). Thai PHIV male adolescents had a higher incidence of HR-HPV infection than those without HIV. Having multiple sex partners and co-infection with sexually transmitted infections was associated with persistent HR-HPV infection. These data demonstrate the need to prioritize PHIV male adolescents in routine and catch-up HPV vaccination programs.

Incidence, clearance, persistence and factors related with high-risk anal HPV persistence in South-East Asian MSM and transgender women.

Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence. Prospective cohort study. MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence. Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence. HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya

Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes. This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks. In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P = 0.044). High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.

The Accuracy of Anal Swab-Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis.

BackgroundThe incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients.MethodsWe searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN).ResultsWe included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%).ConclusionsGiven its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

P16 as an independent marker for detection of high-risk HPV in oral submucous fibrosis and oral squamous cell carcinoma.

An alarming increase in incidence of high-risk human papillomavirus (HPV) positive tumors in head and neck squamous cell carcinoma (HNSCC) by 25% and 70% in oropharyngeal HNSCC cannot be ignored. The early oncogenes of HPV, E6, and E7 play a key role in carcinogenesis. HPV associated tumors have a better clinical outcome and a favorable prognosis. The p16 expression has high concordance with other methods of HPV detection, ascertaining p16 as a surrogate marker for HPV. To assess the immunohistochemical expression of p16 in oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) with and without coexistent OSF as a marker for high-risk HPV detection. Materials and. Tissue blocks of 70 cases including normal, OSF, OSCC with and without OSF were subjected to IHC staining with a p16INK4A monoclonal antibody. (Biogenex, San Roman). The p16 expression was noted according to percent positivity and pattern. The data were tabulated, statistically analyzed using the Chi-square test and the P value was assessed. The percentage of p16 positive cells raised from normal to OSF to OSCC with and without OSF. In addition, a shift from nuclear to cytoplasmic expression from normal to OSCC was noted with a statistical significance (P < 0.001). However, no statistical significance was established with any clinicopathologic parameters except age (P = 0.012) and habits (P= 0.023). The presence of HPV using p16 was not detected in OSF but was positive in OSCC. Altered pattern of expression from normal to OSF to OSCC indicates promising use of p16 as a diagnostic marker.

Human Papillomavirus Types and Cervical Cancer Vaccine for Sudanese Women: A Review

Cervical cancer is thought to result from different high-risk human papillomavirus (HPV) types. Although many studies have been conducted worldwide regarding HPV infection and its oncogenic properties, limited data are available on the incidence and genotype specific dissemination of HPV in Sudan. The purpose of this review article is to summarize the existing data regarding HPV genotypes in Sudan. To review the distribution of HPV infections, electronic databases (e.g. PubMed, and Google Scholar) were searched for peer reviewed articles in English. The study was performed between January and April of 2019 and comprises a review of six relevant articles that were published prior to 2013. Inclusion criteria included: availability of general population data, cytology and tissue results and the use of polymerase chain reaction (PCR) for HPV detection. The overall infection rate of high-risk HPVs DNA was 173/506 (34%) and within the tissues ranged between 93 and 94% (all the paraffin sections were cancer and precancerous cases). The HPV genotyping in cervical smears were found to range from 2.9% to 50.0%, with the most prevalent types of HPV being 16 (2.9-50.0%), 18 (0-3.4%), 58 (2.9%), and 42 (2.9%). Familiarity of the frequent high risk HPV genotypes found in Sudan, which had a high prevalence of cervical cancer, is essential in order to construct an applicable genotype of the virus in the HPV vaccine. The commercially available vaccines do not prevent infection of the HPV types not contained in the vaccine. Based on this literature, it is clear that the nine-valent HPV vaccine should be considered in Sudan.

Incidence, Clearance, and Persistence of Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Implications for Human Papillomavirus Vaccination.

Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.

Prevalence and Incidence of Anal and Cervical High-Risk Human Papillomavirus (HPV) Types Covered by Current HPV Vaccines Among HIV-Infected Women in the SUN Study.

Nonavalent (9v) human papilloma virus vaccine targets high-risk human papillomavirus (HR-HPV) types 16, 18, 31, 33, 45, 52, 58, and low-risk 6, 11. We examined prevalence, incidence, and clearance of anal and cervical HR-HPV in HIV-infected women. The SUN Study enrolled 167 US women in 2004-2006. Anal and cervical specimens were collected annually for cytology and identification of 37 HPV types: 14 HR included: 9v 16, 18, 31, 33, 45, 52, 58; non-9v 35, 39, 51, 56, 59, 66, 68. Baseline characteristics of 126 women included: median age 38 years; 57% non-Hispanic black; 67% HIV RNA < 400 copies/mL; 90% CD4 counts ≥200 cells/mm3. HPV prevalence at anus and cervix was 90% and 83%; for 9v HR-HPV types, 67% and 51%; non-9v HR-HPV, 54% and 29%, respectively. The 9v and non-9v HR-HPV incidence rates/100 person-years were similar (10.4 vs 9.5; 8.5 vs 8.3, respectively); 9v clearance rates were 42% and 61%; non-9v 46% and 59%, in anus and cervix, respectively. Anal HR-HPV prevalence was higher than cervical, with lower clearance; incidence was similar. Although prevalence of non-9v HR-HPV was substantial, 9v HR-HPV types were generally more prevalent. These findings support use of nonavalent vaccine in HIV-infected women.