Coinfections in human papillomavirus associated cancers and prophylactic recommendations.

The Human Papillomavirus (HPV) infection is responsible for more than 80% of reported cervical cancer and other virus-associated tumours. Although this global threat can be controlled using effective vaccination strategies, a growing perturbation of HPV infection is an emerging coinfection likely to increase the severity of the infection in humans. Moreover, these coinfections prolong the HPV infections, thereby risking the chances for oncogenic progression. The present review consolidated the clinically significant microbial coinfections/co-presence associated with HPV and their underlying molecular mechanisms. We discussed the gaps and concerns associated with demography, present vaccination strategies, and other prophylactic limitations. We concluded our review by highlighting the potential clinical as well as emerging computational intervention measures to kerb down HPV-associated severities.

Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.

High Risk of New HPV Infection Acquisition Among Unvaccinated Young Men.

BACKGROUND: International data on anogenital HPV infection incidence among men are limited. METHODS: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months. RESULTS: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%). CONCLUSIONS: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285.

Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.

BACKGROUND: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined. METHODS: We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results. RESULTS: In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0). CONCLUSIONS: Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.

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.

Cost-effectiveness of primary human papillomavirus triage approaches among vaccinated women in Norway: A model-based analysis.

As Norway considers revising triage approaches following their first adolescent cohort with human papillomavirus (HPV) vaccination entering the cervical cancer screening program, we analyzed the health impact and cost-effectiveness of alternative primary HPV triage approaches for women initiating cervical cancer screening in 2023. We used a multimodeling approach that captured HPV transmission and cervical carcinogenesis to evaluate the health benefits, harms and cost-effectiveness of alternative extended genotyping and age-based triage strategies under five-yearly primary HPV testing (including the status-quo screening strategy in Norway) for women born in 1998 (ie, age 25 in 2023). We examined 35 strategies that varied alternative groupings of high-risk HPV genotypes ("high-risk" genotypes; "medium-risk" genotypes or "intermediate-risk" genotypes), number and types of HPV included in each group, management of HPV-positive women to direct colposcopy or active surveillance, wait time for re-testing and age at which the HPV triage algorithm switched from less to more intensive strategies. Given the range of benchmarks for severity-specific cost-effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved an age-based switch from a less to more intensive follow-up algorithm at age 30 or 35 years with HPV-16/18 genotypes in the "high-risk" group. The two potentially cost-effective strategies could reduce the number of colposcopies compared to current guidelines and simultaneously improve health benefits. Using age to guide primary HPV triage, paired with selective HPV genotype and follow-up time for re-testing, could improve both the cervical cancer program effectiveness and efficiency.

High-risk human papillomavirus distribution according to human immunodeficiency virus status among women with cervical cancer in Abidjan, Côte d'Ivoire, 2018 to 2020.

As human papillomavirus (HPV) immunisation and HPV-based cervical cancer (CC) screening programmes expand across sub-Saharan Africa, we investigated the potential impact of human immunodeficiency virus (HIV) status on high-risk (HR)-HPV distribution among women with CC in Côte d'Ivoire. From July 2018 to June 2020, paraffin-embedded CC specimens diagnosed in Abidjan, Côte d'Ivoire were systematically collected and tested for HR-HPV DNA. Type-specific HR-HPV prevalence was compared according to HIV status. Of the 170 CC specimens analysed (median age 52 years, interquartile range: [43.0-60.0]), 43 (25.3%) were from women living with HIV (WLHIV) with a median CD4 count of 526 [373-833] cells/mm3 and 86% were on antiretroviral therapy (ART). The overall HR-HPV prevalence was 89.4% [95% CI: 84.7-94.1]. All were single HR-HPV infections with no differences according to HIV status (P = .8). Among HR-HPV-positive CC specimens, the most prevalent HR-HPV types were HPV16 (57.2%), HPV18 (19.7%), HPV45 (8.6%) and HPV35 (4.6%), with no significant differences according to HIV status. Altogether, infection with HPV16/18 accounted for 71.1% [95% CI: 55.9-86.2] of CC cases in WLHIV vs 78.9% [95% CI: 71.3-86.5] in women without HIV (P = .3). The study confirms the major role of HPV16/18 in CC in Côte d'Ivoire and should support a regional scale-up of HPV16/18 vaccination programmes regardless of HIV status. However, vaccines targeting additional HR-HPV types, including HPV45 and HPV35, could further decrease future CC incidence in Côte d'Ivoire, both for WLHIV and women without HIV.

Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.

Long-term follow-up of cervical cancer incidence after normal cytological findings.

An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.

Cervical precancer and cancer incidence among insured women with and without HIV in South Africa.

HIV infection increases the risk of developing cervical cancer; however, longitudinal studies in sub-Saharan Africa comparing cervical cancer rates between women living with HIV (WLWH) and women without HIV are scarce. To address this gap, we compared cervical precancer and cancer incidence rates between WLWH and women without HIV in South Africa using reimbursement claims data from a medical insurance scheme from January 2011 to June 2020. We used Royston-Parmar flexible parametric survival models to estimate cervical precancer and cancer incidence rates as a continuous function of age, stratified by HIV status. Our study population consisted of 518 048 women, with exclusions based on the endpoint of interest. To analyse cervical cancer incidence, we included 517 312 women, of whom 564 developed cervical cancer. WLWH had an ~3-fold higher risk of developing cervical precancer and cancer than women without HIV (adjusted hazard ratio for cervical cancer: 2.99; 95% confidence interval [CI]: 2.40-3.73). For all endpoints of interest, the estimated incidence rates were higher in WLWH than women without HIV. Cervical cancer rates among WLWH increased at early ages and peaked at 49 years (122/100 000 person-years; 95% CI: 100-147), whereas, in women without HIV, incidence rates peaked at 56 years (40/100 000 person-years; 95% CI: 36-45). Cervical precancer rates peaked in women in their 30s. Analyses of age-specific cervical cancer rates by HIV status are essential to inform the design of targeted cervical cancer prevention policies in Southern Africa and other regions with a double burden of HIV and cervical cancer.

The impact of loss to follow-up in the Dutch organised HPV-based cervical cancer screening programme.

Loss to follow-up (LTFU) within cervical screening programmes can result in missed clinically relevant lesions, potentially reducing programme effectiveness. To examine the health impact of losing women during the screening process, we determined the proportion of women LTFU per step of the Dutch hrHPV-based screening programme. We then determined the probability of being LTFU by age, screening history and sampling method (self- or clinician-sampled) using logistic regression analysis. Finally, we estimated the number of missed CIN2+/3+ lesions per LTFU moment by using the CIN-risk in women compliant with follow-up. Data from the Dutch nationwide pathology databank (Palga) was used. Women eligible for screening in 2017 and 2018 were included (N = 840,428). For clinician collected (CC) samples, the highest proportion LTFU was found following 'referral advice for colposcopy' (5.5% after indirect referral; 3.8% after direct referral). For self-sampling, the highest proportions LTFU were found following the advice for repeat cytology (13.6%) and after referral advice for colposcopy (8.2% after indirect referral; 4.3% after direct referral). Self-sampling users and women with no screening history had a higher LTFU-risk (OR: 3.87, CI: 3.55-4.23; OR: 1.39, CI: 1.20-1.61) compared to women that used CC sampling and women that have been screened before, respectively. Of all women LTFU in 2017/18, the total number of potentially missed CIN2+ was 844 (21% of women LTFU). Most lesions were missed after 'direct referral for colposcopy' (N = 462, 11.5% of women LTFU). So, this indicates a gap between the screening programme and clinical care which requires further attention, by improving monitoring of patients after referral.

Gynaecologic and breast cancers in women living with HIV in South Africa: A record linkage study.

Breast and gynaecologic cancers account for approximately half of all cancers diagnosed amongst women in South Africa, many of whom also live with HIV. We aimed to determine the incidence of and risk factors for developing breast and gynaecologic cancers in women living with HIV (WLHIV) in South Africa. This is a longitudinal analysis of the South African HIV Cancer Match study including women aged ≥15 years with two or more HIV-related laboratory tests. We used Cox proportional hazard models to determine the association of Human Papilloma Virus (HPV)-related and hormone-related gynaecologic cancer with patient- and municipal-level characteristics. From 3 447 908 women and 10.5 million years of follow-up, we identified 11 384 incident and 7612 prevalent gynaecologic and breast cancers. The overall crude incidence rate was 108/1 00 000 person-years (pyears) (95% confidence interval [CI]: 106-110), with the highest incidence observed for cervical cancer (70/1 00 000 pyears; 95% CI: 68.5-71.7). Low CD4 cell counts and high HIV RNA viral loads increased the risk of cervical and other HPV-related cancers. Age was associated with both HPV-related and hormone-related cancers. Women accessing health facilities in high socioeconomic position (SEP) municipalities were more likely to be diagnosed with HPV-related cancers and breast cancer than women accessing care in low SEP municipalities. It is important to improve the immunologic status of WLHIV as part of cancer prevention strategies in WLHIV. Cancer prevention and early detection programmes should be tailored to the needs of women ageing with HIV. In addition, SEP disparities in cancer diagnostic services have to be addressed.

Effectiveness of self-sampling human papillomavirus test on precancer detection and screening uptake in Japan: The ACCESS randomized controlled trial.

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections.

Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Evidence-Based Storytelling for a Strategic Roadmap to Promote Cancer Prevention via Adolescent HPV Vaccination in Northern New England.

Vaccination rates for the human papillomavirus (HPV) among rural youth in northern New England lag those of more urbanized areas. Reasons include a lack of available medical offices, time constraints, perceptions of vaccines and HPV, and, to a smaller degree, delays caused by the COVID-19 pandemic. We have a responsibility to increase vaccinations in these communities. To do so, vaccination experts recommend addressing the three C's of vaccination hesitation: confidence, complacency, and convenience. With this framework as our foundation, in this article we detail a plan to address these important elements, and we add several more C's: clinics, communication, collaboration, community, capacity, and commitment to the list as we discuss the essential pieces-human, infrastructural, and perceptual-needed to create and promote successful, community-supported, school-based HPV vaccination clinics to serve youths aged nine to 18. We then integrate research and storytelling science into an innovative Persuasion Playbook, a guide for local opinion leaders to use in creating evidence-based, pro-vaccine messages on the community level to promote the clinics via evidence-based, pro-vaccination messages.

Vaccination and screening strategies to accelerate cervical cancer elimination in Norway: a model-based analysis.

BACKGROUND: Experts have proposed an 'EVEN FASTER' concept targeting age-groups maintaining circulation of human papillomavirus (HPV). We explored effects of the vaccination component of these proposals compared with cervical cancer (CC) screening-based interventions on age-standardized incidence rate (ASR) and CC elimination (<4 cases/100,000) timing in Norway. METHODS: We used a model-based approach to evaluate HPV vaccination and CC screening scenarios compared with a status-quo scenario reflecting previous vaccination and screening. For cohorts ages 25-30 years, we examined 6 vaccination scenarios that incrementally increased vaccination coverage from current cohort-specific rates. Each vaccination scenario was coupled with three screening strategies that varied screening frequency. Additionally, we included 4 scenarios that alternatively increased screening adherence. Population- and cohort-level outcomes included ASR, lifetime risk of CC, and colposcopy referrals. RESULTS: Several vaccination strategies coupled with de-intensified screening frequencies lowered ASR, but did not accelerate CC elimination. Alternative strategies that increased screening adherence could both accelerate elimination and improve ASR. CONCLUSIONS: The vaccination component of an 'EVEN FASTER' campaign is unlikely to accelerate CC elimination in Norway but may reduce population-level ASR. Alternatively, targeting under- and never-screeners may both eliminate CC faster and lead to greater health benefits compared with vaccination-based interventions we considered.

CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by the gain of function of the CXCR4 chemokine receptor. We present the prevalence of cancer in WHIMS patients based on data from the French Severe Chronic Neutropenia Registry and an exhaustive literature review. The median follow-up of the 14 WHIMS 'patients was 28.5 years. A central review and viral evaluation of pathological samples were organized, and we conducted a thorough literature review to identify all reports of WHIMS cases. Six French patients were diagnosed with cancer at a median age of 37.6 years. The 40-year risk of malignancy was 39% (95% confidence interval [CI]: 6%-74%). We observed two human papillomavirus (HPV)-induced vulvar carcinomas, three lymphomas (two Epstein-Barr virus [EBV]-related) and one basal cell carcinoma. Among the 155 WHIMS cases from the literature, 22 cancers were reported in 16 patients, with an overall cancer 40-year risk of 23% (95% CI: 13%-39%). Malignancies included EBV-associated lymphoproliferative disorders and HPV-positive genital and anal cancers as in the French cohort. Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.