This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18–35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007–2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%–25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18–22 years (VE = 64%) and 23–27 years (65%). Among participants aged 18–22 years vaccinated before sexual debut, the VE was 47% (23%–64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%–77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5–10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs.-prevaccine and vaccinated-vs.-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs.-prevaccine than in the vaccinated-vs.-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence.

In 2015, Botswana introduced the quadrivalent human papillomavirus (HPV) vaccine as a two-dose schedule in girls aged 9–13 years. We sought to establish a baseline HPV prevalence in unvaccinated young adults in Botswana. HIV-uninfected men and women aged 18–22 years were recruited from the University of Botswana in Gaborone during October 2019–February 2021. Demographic and behavioural characteristics were self-reported during structured interviews. Self-collected vaginal and penile swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared any HPV type, quadrivalent vaccine (HPV 6, 11, 16, 18)-type and non-quadrivalent vaccine-type prevalence in men and women and evaluated the risk factors for prevalence of any HPV type. A total of 493 men and 500 women were included in the analysis. Compared to men, women had higher prevalence of any HPV type (63.0% versus 31.4%, P < 0.001), vaccine-type HPV (21% versus 9.7%, P < 0.001) and non-vaccine-type HPV (60.4% versus 28.4%, P < 0.001). Higher prevalence of any HPV type in men and women was associated with having ≥2 sex partners in the past 12 months; always using condoms in the past 3 months was associated with a lower HPV prevalence. These data provide baseline information for future evaluation of the population impact of the HPV vaccination programme, including potential herd effects in men.

This study aimed to evaluate the performance of Cobas human papillomavirus (HPV) test in cervical cancer screening. A total of 3442 women aged ⩾20 years used Cobas HPV and hybrid capture 2 (HC2) tests were included in this study. Women with any positive result were examined by liquid-based cytology (LBC) test. Then subjects with abnormal LBC or positive Cobas HPV16/18 were further checked by colposcopy to observe the visible lesions to perform the pathological examination. Of these 3442 women, 328 cases were Cobas HPV positive, and the positive rate was 9.53% (95% confidence interval (CI) 8.50–10.53). The positive rate of HPV16, HPV18, and other 12 types of high-risk HPV were 1.54% (95% CI 1.12–1.95), 0.55% (95% CI 0.30–0.80), and 7.44% (95% CI 6.56–8.32), respectively. The coincidence rate of Cobas HPV test and HC2 test was 90% (95% CI 89.00–91.00; Kappa = 0.526) in the primary screening. Age had a non-linear relationship with Cobas HPV positive rate (χ2 = 4.240, P = 0.040) and HPV16/18 typing positive rate (χ2 = 6.610, P = 0.010). Compared with the LBC test, the Cobas HPV test had higher sensitivity when detecting patients with high cervical intraepithelial neoplasia (CIN2+ and CIN3+).

The present study attempted to analyse human papillomavirus (HPV) genotype distribution and its association with cervical cytology results in women in western China. The present retrospective analysis was performed in 1089 female outpatients with a positive HPV test result who had undergone a cervical cytology test at the gynaecological clinic, West China Second Hospital, Sichuan University, China, between January 2014 and December 2016. Of the 1089 patients with HPV infection, multiple HPV genotypes were detected in 220 patients (20.20%). Among the 1368 HPV genotypes detected, 1145 (83.70%) were high-risk subtypes. The most common genotypes were HPV-52 (18.64%), HPV-16 (16.59%), HPV-58 (13.23%), HPV-18 (6.80%), HPV-56 (5.56%) and HPV-59 (5.56%). Cervical cytology revealed abnormal cells in 430 (39.49%) patients. The most common diagnoses were atypical squamous cells of undetermined significance (ASC-US; 236 cases, 54.88%), low-grade squamous intraepithelial lesions (LSIL; 151 cases, 35.12%), high-grade squamous intraepithelial lesions (HSIL; 63 cases, 14.65%) and atypical glandular cells (AGC; 21 cases, 4.88%). HPV-66 was significantly associated (P = 0.037) with ASC; HPV-52 and HPV-56 were significantly associated with LSIL (P = 0.009 and 0.026, respectively); HPV-16 (P < 0.001), HPV-33 (P = 0.014) and HPV-58 (P = 0.003) were significantly associated with HSIL; and HPV-16 (P = 0.005) was significantly associated with AGC. HPV-16, HPV-52 and HPV-58 are associated with different diagnoses in patients with positive cervical cytological findings.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness to radiotherapy. The increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and repair of DNA double-strand breaks. Therefore, strategies to further radiosensitise HPV-positive HNSCC, but also radioresistant HPV-negative HNSCC, have focussed on targeting key DNA repair proteins including PARP, DNA-Pk, ATM and ATR. However, inhibitors against CHK1 and WEE1 involved in cell-cycle checkpoint activation have also been investigated as targets for radiosensitisation in HNSCC. These studies, largely conducted using established HNSCC cell lines in vitro, have demonstrated variability in the response dependent on the specific inhibitors and cell models utilised. However, promising results are evident targeting specifically PARP, DNA-Pk, ATR and CHK1 in synergising with radiation in HNSCC cell killing. Nevertheless, these preclinical studies require further expansion and investigation for translational opportunities for the effective treatment of HNSCC in combination with radiotherapy.

Our purpose was to determine the effectiveness and harms of vaccination in patients with any sexual history to prevent the prevalence of papillomavirus infection. A search strategy was conducted in the MEDLINE, CENTRAL, EMBASE and LILACS databases. Searches were also conducted in other databases and unpublished literature. The risk of bias was evaluated with the Cochrane Collaboration's tool. Analysis of fixed effects was conducted. The primary outcome was the infection by any and each human papillomavirus (HPV) genotype, serious adverse effects and short-term adverse effects. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were bivalent vaccine/tetravalent/nonavalent vs. placebo/no intervention/other vaccines. We included 29 studies described in 35 publications. Bivalent HPV vaccine offers protection against HPV16 (RD −0.05, 95% CI −0.098 to −0.0032), HPV18 (RD −0.03, 95% CI −0.062 to −0.0004) and HPV16/18 genotypes (RD of −0.1, 95% CI −0.16 to −0.04). On the other side, tetravalent HPV vaccine offered protection against HPV6 (RD of −0.0500, 95% CI −0.0963 to −0.0230), HPV11 (RD −0.0198, 95% CI −0.0310 to −0.0085). Also, against HPV16 (RD of −0.0608, 95% CI −0.1126 to −0.0091) and HPV18 (RD of −0.0200, 95% CI −0.0408 to −0.0123). There was a reduction in the prevalence of HPV16, 18 and 16/18 genotypes when applying the bivalent vaccine, with no increase in adverse effects. Regarding the tetravalent vaccine, we found a reduction in the prevalence of HPV6, 11, 16 and 18 genotypes, with no increase in adverse effects.

Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer and the prevalence of HPV types varies depending on the geographic region. Therefore, this study assessed the prevalence of HPV types in women with cervical lesions from Sergipe state, Northeastern Brazil. A cross-sectional study was conducted in women with cervical lesions from March to December 2014. These lesions were investigated by PCR and HPV types were identified by DNA sequencing. 432 patients were included, of which 337 patients tested positive for HPV. Eighteen different HPV types were detected, and high-risk HPV types were detected in 69.2%. HPV 16 (63.4%) was the most prevalent HPV type found, followed by HPV 66 (4.6%), HPV 18 (1.6%) and HPV 45 (1.4%). These results highlight the importance of the high prevalence of HPV 66, which is a possibly carcinogenic virus type not covered by the available vaccines. The prevalence of HPV 16 was high in the studied population, reaffirming the importance of young vaccination. However, the high prevalence of HPV 66 found in this study shows the importance of monitoring the diversity of HPV types in different populations and geographic regions to better understand the impacts of current HPV vaccines.

Background: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. Methods/Design: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. Discussion: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.

The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13·7% vs. 6·9%, P < 0·05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24·4% and the cumulative incidence was 24·1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58·3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations.

Human papillomavirus (HPV) types 6 and 11 are the aetiological agent of recurrent respiratory papillomatosis (RRP). The complete genome of an HPV6 isolate with a 170 base pair (bp) duplication identified within the long control region (LCR) from a patient with aggressive recurrent respiratory papillomatosis was determined. The promoter sequence from the HPV LCR including the 170 bp duplication was placed upstream of a heterologous reporter gene and the activity of the reporter gene product determined using transfected cells. In total, mutations were observed at 157 nucleotide positions of the complete genome and included nucleotide substitutions, deletions and insertions, resulting in amino acid changes at 43 residue positions. Reporter gene activity using an HPV-derived LCR region with a 170 bp duplication was significantly higher than that using an HPV-derived LCR region with no duplication within this region. The results suggest that novel HPV variants warrant further investigation for potential biomarkers of aggressive disease.