Introduction

Estimates of cervical cancer (CC) fractions attributable to HPV genotypes are essential to inform CC prevention programmes, but are hampered because of confounding by sharing common transmission routes and distinguishing causal types in multiple HPV infections.

Methods

We performed a systematic review and meta-analysis, including 917 studies with 90,353 CC and 1,663,790 cytologically normal controls. Type-specific odds ratios (ORs) of HPV prevalence in cases versus controls were calculated by multivariate generalized linear models (GLM), adjusted for region and HIV status. Types with OR>1 were judged as attributable. Regional attributable fractions (AFs) were calculated as prevalence in CC multiplied by (1-1/OR). Global AFs were calculated from regional AFs weighted by regional CC burden in 2020 (GLOBOCAN). AFs were proportionally adjusted to sum to 100%.

Results

Nineteen types were attributable to CC. HPV16 had highest global AF (60.6%), followed by HPV18(16.2%), HPV45(5.6%), HPV33(3.6%), HPV58(3.3%), HPV52(2.5%), HPV31(2.0%), and HPV35(1.5%). The remaining attributable types (HPV59, HPV39, HPV56, HPV73, HPV51, HPV26, HPV68, HPV30, HPV67, HPV69, and HPV82) had individual AFs <1%, and a combined AF of 4.7%. For each region, HPV16 and 18 were the most attributable types, with a combined AF of 73.5% in Eastern Asia, 76.9% in Africa, 76.3% in Southern/Western Asia, 82.5% in North America, 83.0% in Europe, 83.5% in Central/South America, and 91.7% in Oceania, respectively. The third most attributable type was HPV45 in Oceania (4.5%), North and Central/South Americas (each 5.4%), Southern/Western Asia (6.3%) and Africa (9.9%), but HPV33 in Europe (4.7%) and HPV58 in Eastern Asia (8.0%). AF of HPV35 was higher in Africa (3.1%) than in other regions (0.7-1.6%). Combined HPV16/18/31/33/45/52/58 AF was >93% in every region.

Conclusions

This novel methodological approach, based on up-to-date and large meta-analytic datasets, provides robust estimates of AFs of HPV types causally related to CC, at global and regional levels.

Introduction

Excisional treatment for precancerous cervical lesions has been linked to preterm births (PTBs) in future pregnancies. Women with untreated/pre-treatment precancerous abnormalities, have also been shown to have an increased, albeit lower, risk of PTBs. We examined PTB rates in NSW women with a previous precancerous abnormality, as a benchmark for future HPV vaccination impact studies. Treatment is recommended for most histologically-confirmed high-grade lesions, and many women with low-grade lesions also received treatment prior to changes in recommendations in 2006.

Methods

Using linked data from the NSW Perinatal Data Collection and Pap Test Register, we compared rates of PTBs (<37 weeks gestation) in women with a previous histologically-confirmed high-grade/ low-grade lesion and women with no prior histological abnormalities (previous negative/benign cervical histology or no previous histology recorded) using logistic regression in live singleton births 01/01/2000-30/06/2020. We adjusted for year of birth of infant, and a range of relevant socio-demographic/health/obstetric factors (Table).

Results

Of 9,412,074 live singleton births, 5.51% were preterm (8.11% in women with previous high-grade histology; 7.05% with previous low-grade histology) (Table). Compared to women with no previous abnormality, women with previous high-grade histology (odds ratio [OR] 1.52, 95% confidence interval [95%CI]:1.47-1.58) and previous low-grade histology (OR 1.31, 95%CI:1.26-1.36) were significantly more likely to have a PTB (p<0.001). Increased odds of a PTB post a high-grade (adjusted OR [aOR] 1.39, 95%CI:1.34-1-43) and low-grade (aOR 1.22, 95%CI:1.18-1.27) lesion (p<0.001) remained after adjusting for socio-demographic/health/obstetric factors (Table)

Conclusions

Women with abnormal cervical histology, especially a previous high-grade diagnosis, had increased PTBs in future pregnancies. Excisional treatment hasn’t been recommended for women with low-grade histology since 2006. Ongoing analysis is examining whether women with low-grade lesions who were less likely to receive treatment (i.e., after 2006) were also at increased risk of PTB, which may relate to HPV infection itself, residual confounding or other factors.

Introduction

Objectives:

To compare the prevalence of syphilis, hepatitis B, hepatitis C, HIV and high-risk HPV co-infection and associated factors among two cohorts (2009 and 2019) of female sex workers (FSWs) receiving care at a Women’s health clinic in Mumbai, India.

Methods

We performed a retrospective cohort study. All consecutive FSWs 18 years and older during the years 2009 and 2019 who consented were eligible for inclusion. Participants were clinically evaluated using blood, vaginal and endocervical swabs for at least five STIs: high-risk HPV (HR-HPV), HCV, HBV, HIV, and syphilis. The difference in demographic characteristics and HPV/STI co-infection patterns between the 2009 and 2019 cohorts was assessed using binary logistic regression, chi-square test or Mann-Whitney U test (as applicable).

Results

Altogether, 300 participants in the 2009 cohort and 400 in the 2019 cohort met the eligibility criteria. There was a statistically significant difference between the 2009 and 2019 cohort for age (30 years versus 33 years, p=0.002), and condom usage (74% versus 99%, p<0.001). There was a statistically significant decline in the prevalence of syphilis (40% versus 14%, p<0.001), HBV (40% versus 14%, p=0.02), HCV (3% versus 0.5%, p=0.02), HPV/HIV co-infection (26% versus 16%, p=0.003). The decline in HPV infection prevalence from 2009 to 2019 (40% versus 38%, p=0.53) was not statistically significant. All the results remained unchanged when adjusted for age and condom use.

Conclusions

The significant decline in syphilis, HBV, HCV, and HPV/HIV coinfection prevalence among FSWs in Mumbai is possibly due to the success of targeted intervention programs for key populations in India. Cervical cancer screening must be launched and bundled with STI screening given the high HPV infection prevalence among these women. The indigenously crafted Indian HPV vaccine Cervavac may protect this high-risk population from future cervical disease and may also reduce transmission risk.

Introduction

Human papillomavirus (HPV) infections sometimes have intermittent positivity detection patterns. We assessed the cumulative incidence of redetection with the same HPV type, predictors of first HPV detections compared with redetections, and prevalence of cytological abnormalities during redetection episodes with the same HPV type.

Methods

The Ludwig-McGill cohort study followed-up women aged 18-60 years recruited in São Paulo, Brazil in 1993-1997 at visits 4-6 months apart for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. HPV DNA was extracted and amplified by PCR using the MY09/11 and PGMY protocols, with genotyping of over 40 HPV types. A redetection was defined as a recurring type-specific HPV positive result after one or more intervening negative visits. Predictors of type-specific redetection were assessed using Cox regression modeling, with the observation level being the HPV type.

Results

2184 women contributed 2368 incident HPV type-specific first detections and 308 redetections over a median of 6.5 years of follow-up. The cumulative incidence of redetection with the same type was 7% (95%CI 6-8%) 1 year after the clearance of the first detection, and 15% (95%CI 13-17%) 5 years after the clearance of the first detection (average over all HPV types). There were differences in redetection probabilities across HPV types (p<0.0001), with HPV72 & 62 having the highest redetection probability of all types. Age and new sexual partner acquisition were strong risk factors for first HPV detections but were not statistically associated with type-specific redetection. The prevalence of high-grade squamous intraepithelial lesions was similar across visits with first detections and subsequent redetections with the same type.

Conclusions

Redetections of the same HPV type after one or more intervening negative results were common. Our findings suggest many HPV redetections were likely reactivations of latent recurring infections.

Introduction

In the United States (US) oropharyngeal squamous cell carcinoma is the most frequent HPV-associated cancer, surpassing cervical cancer. Oral HPV prevalence and genotype distribution can inform the burden of HPV-related head and neck diseases and planning of effective prevention programs. This study assessed oral HPV prevalence and risk factors in a general US population.

Methods

Between November 2021 and March 2022, 18–60-year-olds were recruited from 42 dental offices across the US. Participants provided oral rinse and gargle specimen for HPV-DNA detection and genotyping and completed sociodemographic and behavioral questionnaires. HPV-DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 system at a central laboratory.

Results

Of the 3,180 participants enrolled, 55.4% were women, with a median age of 40; 12.2% self-reported having received HPV vaccination. Oral HPV prevalence was 6.5% for any detected genotype, 2% for high-risk types, 1.5% for HPV types in the 9-valent HPV vaccine, and 0.7% for HPV16. Among oral HPV positive participants, HPV 16 was the most prevalent genotype (10.6%) followed by HPV 51 (7.2%) and HPV 66 and 44 (both 5.8%). HPV prevalence was higher in men (9.0%) than women (4.5%), and increased with age with 3.1%, 5.5%, 5.1% and 11.8% prevalence among ages 18-30, 31-40, 41-50 and 51-60, respectively. When stratified by sex and age, HPV was most commonly detected among men aged 51-60 (16.8%). Factors significantly associated with any oral HPV infection included sex, age, smoking status, lifetime number of sex partners, and presence of periodontal disease.

Conclusions

The highest oral HPV burden was among older men, highlighting the need to increase HPV prevention efforts among males. Prevalence and risk factors in the US will be compared to PROGRESS studies currently being conducted in Europe and China using similar methodologies to increase knowledge of the global oral HPV burden.

Introduction

Introduction: In Costa Rica (CR) only a single report on head and neck cancer (HNC) incidence trends (1985-2007) has been published and no investigations on the epidemiology of potentially HPV-related and -unrelated HNCs have been done. We examined the age-adjusted incidence rates (IRs) and trends of HNCs and compared incidence trends of potentially HPV-related and -unrelated HNCs to understand HNC in CR.

Methods

Methods: We obtained all available HNC cases for the period 2006-2015 from the National Cancer Registry of CR and the population estimates from the National Institute of Statistics and Census of CR. The analysis was restricted to invasive squamous cell carcinomas (n=1577). IRs and incidence rate ratios were calculated using SEER*Stat software and were age-adjusted to the 2010 Costa Rican population. Joinpoint Regression Analysis program was used to calculate trends and annual percent changes (APCs) in rates.

Results

Results: For all HNCs the age-adjusted IR was 34.02/1,000,000 person-years; 95% CI 32.36, 35.75. Laryngeal cancer was the most common cancer site followed by oral cavity and oropharynx (Table 1). The incidence for all HNCs non-significantly declined (APC= -3.20; 95% CI -6.38,0.09).There was a significant decline in the incidence of nasopharyngeal cancer (APC= -5.86% per year; 95% CI -10.79, -0.66) and laryngeal cancer (APC= -5.41% per year; -9.19,1.47). The incidence trends for hypopharyngeal, oropharyngeal and oral cavity cancers remained stable over time (Figure 1). HNCs were categorized by their potential relatedness to HPV infection. IRs of potentially-HPV-related HNCs tended to trend upward, while HPV-unrelated HNCs tended to trend downward (Figure 2); the difference in these trends was marginally significant (p for parallelism = 0.061).

Conclusions

Conclusions: HNCs are uncommon in CR and decreased over time. We observed a divergent pattern of decreasing HPV-unrelated with increasing HPV-related HNCs. Additional research is needed to understand the role of HPV in HNCs in CR.

Introduction

The incidence of anal cancer has increased over the last five decades and HIV-negative women continue to bear the greatest burden of this disease. The Costa Rica HPV Vaccine Trial (CVT) study tested the efficacy of the HPV vaccine in healthy women. We aimed to describe the women from the CVT referred to high-resolution anoscopy (HRA) based on abnormal anal cytology and anal HPV infection and to identify risk factors for biopsy-confirmed anal high-grade squamous intraepithelial lesions (hHSIL), the anal cancer precursor.

Methods

At year 7 of the CVT, anal samples were collected and tested for abnormal cytology and high-risk HPV 16/18/45 infection (HR-HPV) infection using SPF10-LiPA25. A subset of these women were invited to participate in an anal follow-up study. Women were referred for HRA if they had any abnormal anal cytology or anal HR-HPV at their final study visit. We estimated prevalence ratios (PR) for associations with biopsy-proven hHSIL at first HRA using univariate regression.

Results

Among 1,023 women in CVT in the anal long-term follow-up study (age-range=23–35-years), 56 women were referred to, and attended, at least one HRA visit (Table 1). Among women referred to HRA, 27 (48%) were diagnosed with anal hHSIL. Women referred to HRA were more likely to never have been vaccinated at the year 7 visit (51% vs. 33%;Table 1). Compared to women referred for HRA but not vaccinated against HPV in the CVT, HPV-vaccinated women had a 69% reduction in prevalence of hHSIL (PR=0.3;95%CI=0.1–0.9;p=0.03). Having ³2 or lifetime anal sex partners was associated with nearly 4-fold increased prevalence of hHSIL (PR=3.8;95%CI=1.0–13.9;p=0.04)(Table 2).

Conclusions

HIV-negative women with abnormal anal cytology or anal HPV infection had a high prevalence of anal HSIL. HPV vaccination status and history of anal intercourse provided additional measures of anal HSIL risk.

Introduction

With a global transition to HPV-based screening, the overall effectiveness of primary HPV testing, particularly in those over 50 years, and those soon to exit screening age of eligibility, must be investigated to inform updated recommendations.

Methods

The current analysis includes participants aged ≥50 who participated in the HPV For Cervical Cancer prevention (FOCAL) randomized clinical trial. A total of 6471 women aged ≥50 were randomly allocated to receive liquid-based cytology (LBC) testing (CA: Control Arm) (3248, 50.19%) at baseline and at 24-months or to receive HPV testing (IA: Intervention Arm) (3223, 49.81%) at baseline. Both groups received co-testing (LBC and HPV) at the 48-month exit. Incidence rates and risk ratios for CIN2+ detection at exit were calculated by arm. Additionally, we compared the number of CIN2+ detections missed by cytology alone in the CA to those missed by HPV alone in the IA during the 48-month exit with co-testing.

Results

At exit, those who received HPV testing at baseline had fewer CIN2+ lesions than those who received cytology. Among those with baseline negative results (LBC or HPV), at exit, the CIN2+ incidence rate was 1.61/1000 (95% CI, 0.52,3.76) in the IA compared to 5.36/1000 (95% CI, 3.13,8.59) in the CA, a risk ratio of 0.30 (95% CI,0.11,0.81). Furthermore, at the 48-month exit, cytology every two years missed more cervical pre-cancers (5 cases) than HPV-based screening every four years (0 cases).

Conclusions

In the ≥50 population, those who were HPV negative at baseline had a statistically significant (70%) rate reduction in cervical pre-cancer at the 48-month exit relative to those who were cytology negative. HPV-based screening identifies pre-cancerous lesions earlier and more accurately than cytology. Our findings suggest that including cytology co-testing may not add any additional value in HPV-based screening programs among those ≥50 years old.

Introduction

Head and neck cancers (HNC) represent one of the most common and fatal cancers in Japan. HPV, smoking, and alcohol consumption are known key contributors. Despite decreasing rates of smoking and alcohol consumption, HNC incidence has increased, particularly for oropharyngeal cancers (OPC). This study aimed to assess HPV attributability in HNC at two time periods in Japan.

Methods

BROADEN is a non-interventional, cross-sectional, multi-center study of HNC patients diagnosed in 2008-2009 and 2018-2019. FFPE tumor samples were collected from patients in a consecutive-retrospective manner, using stringent ICD coding to avoid site misclassification. Tumors were centrally tested for presence of HPV-related biomarkers. HPV attributability required at least two positive tests (SPF₁₀ HPV-DNA PCR, p16^ink4a immunohistochemistry, or E6*I HPV-mRNA test) for OPC, and HPV PCR DNA plus mRNA positivity for non-OPC.

Results

Nineteen oncology centers participated, enrolling 1,108 patients with 950 valid and 158 invalid FFPE tumor samples (valid samples included 473 OPC and 477 non-OPC; 435 for 2008-2009 and 515 for 2018-2019). HNC patients were mainly males (82.3%) with mean(SD) age of 65.8(11.8) years at diagnosis, including 42.7% current smokers, 30.5% ex-smokers and 34.5% heavy drinkers. HPV attributability in OPC increased from 44.9% (95%CI: 38.1%-51.8%) in 2008-2009 to 52.1% (95%CI: 45.9%-58.3%) in 2018-2019. In 2008-2009, HPV attributability in nasopharynx and larynx was 3.4% (95%CI: 0.4%-11.7%) and 5% (95%CI: 0.6%-16.9%), respectively; in oral cavity and hypopharynx were 0%. In 2018-2019, HPV attributability in nasopharynx was 7.7% (95%CI: 2.5%-17.0%), and 0% in hypopharynx, larynx, and oral cavity. High-risk HPV genotypes (16/18/31/33/45/52/58) were found in 97.5% of HPV-attributable HNC.

Conclusions

This study aimed to assess the burden of HPV in HNC by applying stringent HNC classification and HPV testing methodology. Results demonstrate the impact of HPV in HNC in Japan, especially in males, and the increase of HPV attributability over time, particularly in OPC.