Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation

The American Cancer Society (ACS) presents an adaptation of the current Advisory Committee on Immunization Practices recommendations for human papillomavirus (HPV) vaccination. The ACS recommends routine HPV vaccination between ages 9 and 12 years to achieve higher on-time vaccination rates, which will lead to increased numbers of cancers prevented. Health care providers are encouraged to start offering the HPV vaccine series at age 9 or 10 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated. Providers should inform individuals aged 22 to 26 years who have not been previously vaccinated or who have not completed the series that vaccination at older ages is less effective in lowering cancer risk. Catch-up HPV vaccination is not recommended for adults aged older than 26 years. The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit.     

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.     

Head and Neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual

Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high‐risk human papillomavirus‐associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes. Other modifications include: the reorganizing of skin cancer (other than melanoma and Merkel cell carcinoma) from a general chapter for the entire body to a head and neck‐specific cutaneous malignancies chapter; division of cancer of the pharynx into 3 separate chapters; changes to the tumor (T) categories for oral cavity, skin, and nasopharynx; and the addition of extranodal cancer extension to lymph node category (N) in all but the viral‐related cancers and mucosal melanoma. The Head and Neck Task Force worked with colleagues around the world to derive a staging system that reflects ongoing changes in head and neck oncology; it remains user friendly and consistent with the traditional tumor, lymph node, metastasis (TNM) staging paradigm. CA Cancer J Clin 2017;67:122–137. © 2017 American Cancer Society.     

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.     

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.     

Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual

Answer questions and earn CME/CNE This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1‐T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1‐T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2018;68:55‐63. © 2017 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.     

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 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.     

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.     

Cancer screening in the United States, 2017: A review of current American Cancer Society guidelines and current issues in cancer screening

Answer questions and earn CME/CNE Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the authors summarize current American Cancer Society cancer screening guidelines, describe an update of their guideline for using human papillomavirus vaccination for cancer prevention, describe updates in US Preventive Services Task Force recommendations for breast and colorectal cancer screening, discuss interim findings from the UK Collaborative Trial on Ovarian Cancer Screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2017;67:100–121. © 2017 American Cancer Society.     

Human papillomavirus vaccine uptake among 18‐ to 26‐year‐old women in the United States

BACKGROUND:

Human papillomavirus (HPV) vaccine uptake among young adult women has been reported to be very low. The authors conducted this study to provide an update on HPV vaccine uptake among 18‐ to 26‐year‐old women.

METHODS:

The authors used the National Health Interview Survey 2010 data to estimate HPV vaccine coverage and their correlates.

RESULTS:

Overall, 22.7% of women initiated (≥1 dose) and 12.7% completed the vaccine (≥3 doses). Thus, about 56% of women who initiated the vaccine completed it. Multivariate logistic regression analyses showed that younger age, unmarried status, Papanicolaou test, influenza vaccine, lifetime vaccines, and HPV vaccine awareness were positively associated with receiving ≥1 and ≥3 doses. In addition, uninsured women were less likely to receive ≥1 dose (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28‐0.84), and blacks (OR, 0.48; 95% CI, 0.23‐0.99) and women with a family income <100% of the federal poverty level (OR, 0.40; 95% CI, 0.21‐0.73) were less likely to receive ≥3 doses. Furthermore, based on vaccine initiators, blacks were less likely than whites to complete the vaccine (OR, 0.29; 95% CI, 0.16‐0.55). Two thirds of unvaccinated women were not interested in future vaccination. Among those who were interested, >76.4% preferred to receive it free or at a lower cost, whereas 20% would pay the full cost of the vaccine.

CONCLUSIONS:

One in 8 women completed the 3‐dose HPV vaccine. Educational and vaccine financing programs are needed to improve the uptake among low‐income minority women who are at increased risk for cervical cancer. Cancer 2013. © 2012 American Cancer Society.     

The new (Version 9) American Joint Committee on Cancer tumor,node, metastasis staging for cervical cancer

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus-associated and human papillomavirus-independent carcinomas.