Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement

Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375–385. © 2016 American Cancer Society.     

Are we missing an opportunity for cancer prevention? Human papillomavirus vaccination for survivors of pediatric and young adult cancers

Survivors of pediatric and young adult cancers remain at risk for subsequent diseases, including those related to human papillomavirus (HPV) infection. Prevention of HPV acquisition through vaccination has become possible over the last decade. HPV vaccines have been shown to be safe and effective, yet rates of vaccination among childhood cancer survivors have remained low. Multiple factors, including stronger advocacy for this intervention from providers, could potentially increase vaccination and lead to lower HPV disease burdens for childhood cancer survivors. Health care providers for survivors of pediatric and adolescent cancers should prioritize counseling for HPV vaccination at follow‐up visits. Cancer 2015;121:3435–43. © 2015 American Cancer Society.     

The predicted impact of vaccination on human papillomavirus infections in Australia

Vaccines based on human papillomavirus (HPV) 16 and 18 virus-like particles have the potential to prevent approximately 70% of cervical cancers. In Australia, public vaccination against HPV commenced in April 2007, and includes routine vaccination of females aged 12-13 years, and a 2-year school and GP-based catch-up in females aged 12-26 years. The objectives of this study were to estimate initial vaccination coverage rates, to describe current patterns of sexual behavior in young females, and to predict the impact of vaccination on HPV16 infections. We reviewed early coverage data, estimating that coverage in 2007/2008 will reach 86% (feasible range 67-90%) for 12- to 13-year-old girls, with lower rates attained in older females. A review of survey data found that the median age of first intercourse in Australian females is 16 years, with approximately 90% of women sexually active at 22 years. Using these data, we performed an analysis of HPV transmission to predict the impact of vaccination on HPV infection rates. The public program is predicted to result in a reduction in the age-standardized incidence of HPV16 infections of 56% by 2010 (feasible range 48-61%), and 92% by 2050 (feasible range 76-95%). Elective vaccination of older women and vaccination of males may provide some incremental gains, but the benefits to women of vaccinating males will be less if coverage of females remains high. In conclusion, the current vaccination program is expected to result in a substantial and rapid reduction in the incidence of HPV16 in Australia.     

Human papillomavirus infections among Hungarian female sex workers

The purpose of this study was to assess the human papillomavirus (HPV) prevalence in cervical, oropharyngeal and anal samples of the high‐risk population of Hungarian female sex workers (FSWs). HPV testing of swab specimens from FSWs (n = 34) using polymerase chain reaction (PCR) methodology was performed. Results were compared with control group (n = 52) matched for age. Questionnaires were used to obtain data regarding participants' sexual behaviour. Data were analysed using SPSS. HPV DNA was detected in at least one location in a great majority of FSWs (82.4%), compared with 46.2% of the general female population (P < 0.05). Both the cervical and the anal samples of sex workers showed higher infection rates than those of controls (64.7% vs. 34.6% and 50.0% vs. 15.4%, respectively, P < 0.05). High‐risk HPV prevalence was also significantly higher in sex workers (55.9% vs. 25.0%, P < 0.05). A significantly higher proportion of FSWs had a history of genital warts (26.5% vs. 3.8%, P < 0.05). The results suggest that condom use may not result in adequate protection from HPV infection. The high infection rates among FSWs should be viewed as a priority group for HPV and cervical cancer prevention programmes since they are sources of HPV infection for the general population.     

Human papillomavirus vaccine and cervical cancer prevention

Cervical cancer is one of the most common types of cancer in women worldwide, with the highest rates observed in underdeveloped countries. In the last decades, its incidence has decreased after the implementation of screening programs, mainly in developed countries. Iinfection with high-risk oncogenic HPV is associated with precancerous lesions and cervical cancer. Advances in the understanding of the role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recomendation of two prophylactic HPV vaccines. This review article provides a summary of the studies related with their development and efficacy.     

The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer

The incidence of oropharyngeal cancer (OPC) is significantly increasing in the United States. Given that these epidemiologic trends are driven by human papillomavirus (HPV), the potential impact of prophylactic HPV vaccines on the prevention of OPC is of interest. The primary evidence supporting the approval of current prophylactic HPV vaccines is from large phase 3 clinical trials focused on the prevention of genital disease (cervical and anal cancer, as well as genital warts). These trials reported vaccine efficacy rates of 89% to 98% for the prevention of both premalignant lesions and persistent genital infections. However, these trials were designed before the etiologic relationship between HPV and OPC was established. There are differences in the epidemiology of oral and genital HPV infection, such as differences in age and sex distributions, which suggest that the vaccine efficacy observed in genital cancers may not be directly translatable to the cancers of the oropharynx. Evaluation of vaccine efficacy is challenging in the oropharynx because no premalignant lesion analogous to cervical intraepithelial neoplasia in cervical cancer has yet been identified. To truly investigate the efficacy of these vaccines in the oropharynx, additional clinical trials with feasible endpoints are needed. Cancer 2016;122:2313–2323 . © 2016 American Cancer Society.     

一例外阴疣状癌中HPV亚型的免疫组织化学研究

目的：探讨ＨＰＶ１６Ｅ６、Ｅ７与外阴疣状癌发病的关系。方法：用过氧化酶标记的链霉卵白素染色法对外阴疣状癌术后病理切片进行免疫组化染色分析。结果：（１）部分表皮细胞质呈空泡状、核固缩，即挖空细胞；（２）在癌组织表皮基底层大部分细胞Ｅ６、Ｅ７均呈强阳性；（３）癌巢细胞ＨＰＶＥ６仅有散在的阳性细胞，ＨＰＶＥ７染色为弱阳性，也可见散在强阳性细胞；（４）癌旁组织的表皮ＨＰＶＥ６、Ｅ７为强阳性，部分区域为中等强度阳性反应。结论：ＨＰＶＥ６及ＨＰＶＥ７蛋白可能与外阴疣状癌的发生相关。     

Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total, with HPV16/18 present in 96% (24 of 25 with 15 of 25 as single infections). Only two of 22 women had concomitant cytology results suggesting glandular abnormality. Colposcopic impressions (25 total) were either negative or indicated squamous lesions only. Of women with AIS, all six in the vaccine cohort and seven of 16 in the placebo cohort were infected at baseline with the same HPV type that was detected in the AIS lesion. Concurrent squamous lesions were detected in 20 of these 22 women. In summary, our findings show that AIS evades colposcopic and cervical cytologic detection. As most AIS lesions were HPV16/18-related, prophylactic HPV vaccination should reduce the incidence of invasive adenocarcinoma.     

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.     

Human papillomavirus genotype detection from archival papanicolaou-stained cervical tests

BACKGROUND:

Archival Papanicolaou (Pap)‐stained cervical cytology tests may be the only source of a clinical sample for the evaluation of previous human papillomavirus (HPV) infection. Pap tests are ideal because the majority of women in countries with comprehensive screening programs would have had several collected and stored.

METHODS:

In the current study, HPV detection and genotyping were compared in samples collected from a conventionally fixed Pap test with those collected using an endocervical brush and collected in PreservCyt (liquid‐based) in 87 women undergoing management for a high‐grade Pap test abnormality. Cytology slides were scanned to create high‐resolution digital images before the removal of cells because the DNA extraction process resulted in the destruction of the cells from the original sample.

RESULTS:

All previously identified high‐grade abnormalities on the Pap tests were detectable on the digital images. β‐globin was detected in all extracted Pap tests, indicating the presence of recoverable, amplifiable DNA. A total of 62 (71.3%) and 59 (67.8%) tests were found to have high‐risk (HR) HPV detected on PreservCyt and fixed Pap test slides, respectively, with >87% concordance for the detection of HR HPV genotypes. Complete HPV genotyping concordance was observed in 62% and was partial in 26% of sample pairs, with very good agreement for HPV types 16 and 18 (κ = 0.850 and 0.903, respectively). Only 1 Pap test slide was found to be positive whereas the PreservCyt had no detectable HPV DNA, demonstrating a low false‐positive rate (1%).

CONCLUSIONS:

The results of the current study confirm that imaging and subsequent HPV detection and genotyping in archival cervical smears can offer accuracy in HPV detection that is comparable to endocervical brush‐collected PreservCyt samples. Cancer (Cancer Cytopathol) 2010;. © 2010 American Cancer Society.     

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin‐fixed paraffin‐embedded samples, HPV DNA detection and genotyping was performed using SPF‐10/DEIA/LiPA₂₅ system (version 1) . A subset of 116 cancers was further tested for p16^INK4a expression, a cellular surrogate marker for HPV‐associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1–91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2–99.4%). Among cancers, the highest prevalence was observed in warty–basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16^INK4a overexpression was found in 95% of HPV DNA‐positive anal cancers. In view of the results of HPV DNA and high proportion of p16^INK4a overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.     

Human papillomavirus vaccine as a new way of preventing cervical cancer: a dream or the future?

Cervical cancer is the major cause of death in women of reproductive age in parts of the developing world. Thanks to the effectiveness of national screening programs, the incidence and mortality rates for cervical cancer have declined dramatically in developed countries. According to many researchers, human papillomavirus (HPV) infection has an important role in the development of cervical neoplasm. The effects of HPV infection on the oncogenesis of cervical carcinoma can be explained to a large degree by the regulation and function of the two viral oncogenes, E6 and E7. About 25 of >80 types infect the genital tract. HPV types are stratified into low, intermediate- and high-risk categories. Today, vaccines are available against many serious human pathogens. It is accepted worldwide that cervical carcinoma is a consequence of infection with HPV viruses. Therefore it is reasonable to assume that vaccine that prevents infection will reduce the incidence of cervical cancer. Virus-like particles are empty viral capsids, and are the leading candidate vaccines for the treatment or prevention of cervical cancer in humans. The HPV type 16 (HPV16) L1 virus-like particle vaccines have been shown to be generally well tolerated and they generate high levels of antibodies against HPV16. Since approximately 50% of cervical cancers are associated with HPV16 infection, the administration of this type of vaccine to young women could reduce the incidence of HPV16 infection, which is related to cervical dysplasia and cervical neoplasm. Vaccination against HPV infection could reduce the risk of infection and, most importantly, decrease the incidence of cervical cancer. A vaccine for cervical cancer is not a dream in the far future, it is happening today.     

Effectiveness of school-based and high-risk human papillomavirus vaccination programs against cervical dysplasia in Manitoba,Canada

The effectiveness of a vaccination program is influenced by its design and implementation details and by the target population characteristics. Using routinely collected population-based individual-level data, we assessed the effectiveness (against cervical dysplasia) of Manitoba's quadrivalent human papillomavirus (qHPV) routine school-based vaccination program and a short-lived campaign that targeted women at high-risk of developing cervical cancer. Females ≥9 years old who received the qHPV vaccine in Manitoba (Canada) between September 1, 2006, and March 31, 2013 (N = 31,442) were matched on age and area of residence to up to three unvaccinated females. Cox proportional hazards models were used to estimate qHPV VE against high-grade (HSILs) and low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUS). Among 14–17-year-old participants who had Pap cytology after enrollment, the adjusted qHPV VE estimates were 30% (17–58%) and 36% (21–48%) against the detection of HSILs and LSILs, respectively. There was, however, no evidence of program effectiveness among females vaccinated at ≥18 years of age and among those with a history of abnormal cytology, who were mostly vaccinated as part of the high-risk program. Estimates of VE for females vaccinated in the school-based program are consistent with the expected benefits from qHPV vaccination. No similar benefits were detected among women vaccinated at an older age, and those with abnormal cytology, who were targeted by the high-risk program. Further efforts should be targeted at achieving higher vaccine coverage among preadolescents, prior to the initiation of sexual activity.     

Human papillomavirus 16 and head and neck squamous cell carcinoma

Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case-control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA. HPV16 seropositivity was associated with 1.5- and 6-fold risks for tumors of the oral cavity and pharynx, respectively. There was a dose response trend for HPV16 titer and increasing risk of HNSCC (p < 0.0001) and HPV16 tumor DNA (p < 0.0001). In cases, HPV16 DNA and seropositivity were significantly associated with sexual activity; odds ratios (ORs) of 12.8 and 3.7 were observed for more than 10 oral sexual partners and ORs of 4.5 and 3.2 were associated with a high number of lifetime sexual partners, respectively. Finally, HPV16 seropositivity and HPV16 tumor DNA were associated with hazard ratios of 0.4 and 0.5, respectively, indicating better survival for HPV positive individuals. HPV16 seropositivity was associated with risk for HNSCC, with greatest risk for pharyngeal cancer. We observed dose response relationships between serology titer and both risk for HNSCC and HPV16 tumor DNA. In cases, HPV16 tumor DNA and positive serology were associated with sexual history and improved disease free survival.     

Human papillomavirus vaccination in survivors of childhood cancer

Effective vaccination is now available to prevent human papillomavirus (HPV), the most common sexually transmitted infection and the cause of cervical cancer, which is the second most common cancer among women worldwide. HPV vaccine uptake is particularly important for females surviving cancer, some of whom are at high risk for HPV complications because of the direct and indirect effects of cancer treatment. Thus, version 3.0 of the Children's Oncology Group's Long‐Term Follow‐Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer recommends HPV vaccination for all eligible females surviving childhood cancer. Because this vaccine was only approved by the US Food and Drug Administration in 2006, little is known regarding the complexity of vaccination uptake among those surviving cancer. The purpose of this article was to describe the HPV vaccine and its usefulness in the survivorship population, provide a rationale for describing cancer survivors as being at increased risk for HPV complications, identify factors associated with HPV vaccination, and discuss the utilization of these predictors in designing strategies to promote adherence to HPV vaccination recommendations within the survivorship context. Cancer 2009. © 2009 American Cancer Society.     

Human papillomavirus tumor infection in esophageal squamous cell carcinoma

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.