Urinary Bladder Carcinoma and Human Papilloma Virus Infection,an Appraisal of Risk

Human papilloma virus (HPV) is a well known risk factor for cancer development in different body sites, involved ‍in the pathogenesis of several intraepithelial lesions and cancers, for example of the upper alimenatry and respiratory ‍tracts and cervix. Urinary bladder carcinoma is a common urological malignancy for which a relationship with ‍human HPV has been indicated, but the results are controversial. Here, the author performed an appraisal of the ‍previous reports on the studies to document correlation between HPV infection, defined as DNA positive, and urinary ‍bladder carcinoma. According to the literature review, 5 reports were recruited for metanalysis, including 239 cases ‍and 52 healthy subjects. The overall HPV DNA positive rates for the patients and healthy control subjects were 25.5 ‍% (61/239) and 11.5 % (6/52), respectively, the odds ratio of 2.6 pointing to potential as a risk factor.     

HPV 16 in multiple neoplastic lesions in women with CIN III

Paraffin embedded material of multiple primary cancers and other hyperplastic tumours from fifteen patients were analyzed by PCR and in situ hybridization for the presence of HPV DNA in the lesions. All patients had also high grade cervical intraepithelial dysplasia (CIN III) and breast carcinomas and were selected from a previous study enrolling 46 women with CIN III and breast carcinomas. HPV 16 was detected by PCR in 8/15 patients (53%), with eleven HPV 16 positive tumours. HPV 16 was detected in two malignant melanomas, one basal cell carcinoma, one squamous cell carcinoma of the vulva, one Bowen disease of the vulva, two high grade vaginal intraepithelial neoplasias, one cancer corporis uteri, one bronchial carcinoma and two lymphomas. Three cases, two high grade vaginal intraepithelial neoplasia and a squamous cell carcinoma of the vulva, were also reported to be positive by in situ hybridization. 5/8 patients (63%) with HPV 16 positive second cancers had also HPV 16 positive breast carcinomas. All fifteen patients with second cancers after CIN III had HPV 16 positive CIN III lesions; 53% of the patients had also a familial cancer history. We assume that HPV 16 may be involved in the development of different second cancers in women with HPV 16 positive CIN III.     

Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica

BACKGROUND: Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. METHODS: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. RESULTS: Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500). CONCLUSIONS: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.     

Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity,oral contraceptives,and tobacco smoking

It is now well established that infection with oncogenic human papillomavirus (HPV) types is the necessary cause of cervical cancer (CC) and its immediate precursor cervical intraepithelial neoplasia 3. However, HPV infection alone may not be sufficient to cause CC, and other exogenous and endogenous factors may exist that, in conjunction with HPV, influence the risk of progression from cervical HPV infection to CC. In this chapter, we review the evidence for the role of parity, oral contraceptive (OC) use, and tobacco smoking in CC. We also discuss limitations and methodologic problems encountered in assessing available data and outline recommendations for future research. Based on key studies on high-grade squamous intraepithelial lesions (HSILs) and CC conducted among HPV-positive women, it can be concluded that high parity, smoking, and less consistently long-term OC use are cofactors that may modulate the risk of progression from HPV infection to HSIL/CC. From a public health point of view, parity seems to be the behavioral cofactor explaining the highest proportion of CC cases among HPV-infected women. Smoking and long-term OC use may have a similar impact in populations that are heavily exposed to HPV and to these cofactors. Large prospective and retrospective cohort studies of HSIL and CC among middle-aged women in which several markers of HPV exposure are used and HPV persistence is documented would be valuable to study the role of these and other cofactors in HPV carcinogenesis. If confirmed, our conclusions may imply that multiparous women, women who are smokers, and women on long-term OC use may need closer surveillance for cytologic abnormalities and HPV infections than women in the general population.     

巴中地区女性体检人群HPV病毒感染情况及对宫颈病变发生率的影响

目的:了解四川省巴中地区女性人乳头瘤病毒(human papillomavirus,HPV)感染情况,分析其型别与宫颈病变的相关性。方法:收集2015年01月至2019年06月在我院进行健康体检的5 046例女性作为研究对象,采用荧光定量PCR法对15种高危HPV基因亚型进行检测,分析是否发生HPV感染及不同HPV亚型对宫颈鳞状上皮内病变的影响。结果:HPV感染率为24.36%(1 229/5 046)。单一HPV感染954例,占全部感染的77.62%,感染率为18.91%;多重HPV感染275例,占全部感染的22.38%,感染率为5.45%。感染率前5位的HPV亚型分别为HPV16(3.86%,195例)、HPV18(3.63%,183例)、HPV52(2.26%,114例)、HPV58(1.61%,81例)、HPV51(1.41%,71例)。≤30岁、31~40岁、41~50岁、>50岁四个年龄组HPV阳性感染率分别为30.28%、22.89%、25.31%、20.00%,各年龄组感染率之间差异有统计学意义(P<0.001)。多重感染患者的高度鳞状上皮内病变的非典型鳞状上皮细胞（ASC-H）、低度鳞状上皮内病变（LSIL）、高度鳞状上皮内病变（HSIL）和鳞状细胞癌（SCC）四种宫颈鳞状上皮内病变的发生比例高于单一感染患者,但差异尚未显示有统计学意义(P=0.608)。结论:巴中地区女性体检人群HPV感染率较高,应加强和普及本地区HPV筛查工作。     

妊娠合并子宫颈上皮内瘤变患者高危型人乳头状瘤病毒感染的临床研究

目的探讨妊娠合并子宫颈上皮内瘤变患者高危型人乳头状瘤病毒（HPV）感染情况。方法将2011年11月至2012年10月间收治的118例妊娠合并子宫颈上皮内瘤变患者（实验组）和118例宫颈健康的妊娠女性（对照组）作为研究对象,比较两组高危型HPV的感染情况。结果妊娠合并宫颈上皮内瘤变（CIN）患者感染的HPV主要类型为HPV16和HPV18,两者在宫颈癌发生发展中可能起重要作用,宫颈病变的级别与HPV的阳性率和载荷量呈显著正相关,两者可以作为妊娠合并CIN患者早期诊断的临床指标之一。结论妊娠合并子宫颈上皮内瘤变患者的高危型HPV感染可以作为诊断宫颈癌的重要要指标,值得临床大力推广。     

Prevalence of human papillomavirus in saliva of women with HPV genital lesions

Background

The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation.

Methods

Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA.

Results

The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes.

Conclusion

This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.

     

Characterization of HPV subtypes not covered by the nine-valent vaccine in patients with CIN 2-3 and cervical squamous cell carcinoma

Background: As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer. Materials and methods: A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed. Results: Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P < 0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively. Conclusion: In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.     

Human Papillomavirus Infection and Anogenital Neoplasia in Human Immunodeficiency Virus-Positive Men and Women

Human immunodeficiency virus (HIV)-positive women have a higher prevalenceof human papillomavirus (HPV) infection in the cervix and anus,as well as squamous intraepithelial lesions (SILs) at thesesites, than do HIV-negative women matched for age and HIV riskfactors. Similarly, HIV-positive homosexual or bisexual men havea higher prevalence of anal HPV infection and anal SIL than doHIV-negative homosexual or bisexual men. In HIV-positive individuals,the prevalence of HPV infection, the proportion infected withmultiple HPV types, and the prevalence of anogenital SILs increasewith decreasing CD4 count. This situation may reflect loss ofsystemic immune response to HPV antigens or local HPV-HIV interactionsat the tissue or cellular level. Despite the high levels ofanogenital SILs, to date, there has not been a significant increasein reported cases of invasive anogenital cancer in HIV-positiveindividuals. However, several years may be required for SILto progress to invasive cancer, and the advent of newer therapiesfor HIV that are expected to prolong survival may paradoxicallyincrease the risk of progression to cancer in individuals withSILs if these lesions do not regress spontaneously and remainuntreated.     

An association between human papillomavirus 16/18 deoxyribonucleic acid in peripheral blood with p16 protein expression in neoplastic cervical lesions

BACKGROUND: Human papillomavirus (HPV) infection plays a crucial role in cervical carcinogenesis. Apart from the detection of p16 protein in cervical tissues, the feasibility of the presence of HPV DNA in peripheral blood being an auxiliary marker of cervical lesions was examined. METHODS: Peripheral blood samples and cervical tissues, from 36 cervical tissues from high-grade squamous intraepithelial lesions (HSIL) and 31 early invasive cervical cancers (EICC), were analyzed for HPV 16/18 DNA and HPV 16/18 E7 mRNA expression, as well as the in situ expressions of p16 and pRb to investigate the in-between associations. RESULTS: The prevalence of HPV 16/18 DNA in patients with EICC was relatively higher than those of HSIL, in both of cervical tissues and peripheral blood. The presence of HPV 16/18 DNA in peripheral blood was positively correlated with that in cervical tissue, as well as with p16 overexpression in cervical tissues together with a significant correlation between E7 mRNA and pRb and p16 protein expressions. DISCUSSION: A positive correlation between the presence of HPV 16 or 18 DNA in peripheral blood and p16 overexpression in tissues of patients with cervical lesions was confirmed. Together with p16 immunostaining in cervical tissues, the detection of high-risk HPV 16 or 18 DNA in peripheral blood may act as an auxiliary biomarker for HPV-associated neoplastic cervical lesions.     

The serological response to papillomaviruses

The antibody response to papillomaviruses is a key determinant of protective immunity. HPV serology is also an important epidemiological tool for the assay of past and present HPV infections and for prediction of HPV-associated cancers and their precursor lesions. This review focuses on the assay of antibody responses to the HPV capsid, its use as a marker of cumulative HPV exposure and surveys how HPV seroepidemiology has been used to elucidate the spread of HPV infection in various populations, the natural history of HPV infection and that exposure to HPV is associated with increased risk for several human cancers.     

Human papillomavirus vaccines in HIV-positive men and women

PURPOSE OF REVIEW: Individuals with HIV are at greater risk of human papillomavirus-related cancers. This report will assess the potential and limitations of vaccines against human papillomavirus in HIV-positive individuals. RECENT FINDINGS: A worldwide meta-analysis of published data established the under-representation of HPV16, and increased prevalence of multiple-type human papillomavirus infections in HIV-positive women. Associations between HIV-related immunodepression, the progression of human papillomavirus infection to cervical lesions, and an increased risk of cervical cancer in women with HIV have also been shown. An increased incidence of human papillomavirus infection in anal and vulvar/vaginal neoplasia has been reported in individuals with HIV. A prophylactic vaccine against HPV6, 11, 16 and 18 has been licensed, and one against HPV16 and 18 is under evaluation. Both have shown efficacy against persistent infection, as well as related human papillomavirus cervical lesions for up to 5 years. Preliminary results have also been reported on therapeutic vaccines, notably for the treatment of cervical intraepithelial neoplasia grades 2 and 3. SUMMARY: The safety and efficacy of human papillomavirus vaccines in individuals with HIV need to be assessed to prevent cervical cancer in current and future generations. Screening for human papillomavirus-related cancer among HIV patients should be undertaken.     

Anal human papilloma viral infection and squamous cell carcinoma: Need objective biomarkers for risk assessment and surveillance guidelines

High grade anal intraepithelial neoplasia due to human papilloma viral (HPV) infections is a precursor lesion for squamous cell carcinoma especially in high risk populations. Frequent examination and anal biopsies remain unpopular with patients; moreover they are also risk factors for chronic pain, scarring and sphincter injury. There is lack of uniform, surveillance methods and guidelines for anal HPV specifically the intervals between exam and biopsies. The aim of this editorial is to discuss the intervals for surveillance exam and biopsy, based on specific HPV related biomarkers? Currently there are no published randomized controlled trials documenting the effectiveness of anal screening and surveillance programs to reduce the incidence, morbidity and mortality of anal cancers. In contrast, the currently approved screening and surveillance methods available for HPV related cervical cancer includes cytology, HPV DNA test, P16 or combined P16/Ki-67 index and HPV E/6 and E/7 mRNA test. There are very few studies performed to determine the efficacy of these tests in HPV related anal pre-cancerous lesions. The relevance of these biomarkers is discussed in this editorial. Longitudinal prospective research is needed to confirm the effectiveness of these molecular biomarkers that include high risk HPV serotyping, P16 immuno-histiochemistry and E6/E7 mRNA profiling on biopsies to elucidate and establish surveillance guidelines.     

Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5/ bio 6 consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human -globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.     

高危型HPV持续感染在宫颈病变中的分布及其影响因素分析

目的 探讨高危型人乳头瘤病毒(HPV)持续感染在宫颈病变中的分布及其影响因素.方法 选取1388例液基细胞学检查异常者进行宫颈病理组织学检查,同时进行高危型HPV检测并随访,分析不同类型HPV感染的分布情况,以及患者的年龄、性伴侣及宫颈病变的家族史情况.结果 1388例患者中,272例为宫颈炎,936例为宫颈上皮内瘤变(CIN),180例为宫颈癌;宫颈炎患者高危型HPV持续感染率为0.74％,低于其他宫颈病变患者(P﹤0.05).222例高危型HPV持续感染患者中,HPV16、HPV18和HPV58的比例分别为53.60％、22.97％和10.36％;宫颈病变患者中高危型HPV检出较多的亚型分别为HPV16、HPV18和HPV58.初次性行为年龄﹤20岁、性伴侣≥2个和有宫颈癌家族史的患者,其高危型HPV持续感染率分别为21.96％、22.94％和21.20％,高于初次性行为年龄≥20岁、性伴侣1个和无宫颈癌家族史患者的13.33％、13.30％和15.2％(P﹤0.05);合并生殖道炎症的患者,其高危型HPV持续感染率为19.17％,高于无生殖道炎症的患者(P﹤0.05).Logistic回归分析结果显示:初次性行为年龄是高危型HPV持续感染的保护因素(OR=0.576,95％CI:0.576～0.817);性伴侣数量(OR=2.188,95％CI:1.647～2.907)和生殖道炎症(OR=1.904,95％CI:1.214～2.986)是高危型HPV持续感染的危险因素.结论 高危型HPV持续感染主要以HPV16、HPV18和HPV58为主,其不仅与宫颈病变有关,还与患者的初次性行为年龄、性伴侣数量和生殖道炎症有一定的关系.     

宫颈高级别病变与HPV感染型别分析

目的探讨HPV在宫颈高级别病变中的感染率及感染型别。方法采用导流杂交法分别检测CINII～Ⅲ30例和宫颈癌患者160例HPV基因型别,比较HPV感染与宫颈病变的关系。结果CINⅡ～III和宫颈癌患者HPV感染率均为90％,且以单型别感染为主,分别为70．37％（19／27）、81．94％（118／144）;在CIN II～Ⅲ中HPV58型、52型感染居多,宫颈癌则以HPV16型、18型感染最常见;无论宫颈鳞癌还是宫颈腺癌,以HPV16型检出率最高。结论HPV16型、18型是宫颈癌的主要致病型,不同病理类型并无HPV型别上的差异;宫颈上皮高级别内瘤变则以HPV58型、52型感染为主;对HPV58型、52型感染者应重视随访。     

Human papillomavirus—the most significant risk determinant of cervical intraepithelial neoplasia

Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions as defined by cytology and 1000 control women selected from an ongoing prospective cohort study in Copenhagen, Denmark. Furthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline case group. At enrollment, all women had a personal interview and a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV testing was performed using a combination of general primer 5/6-mediated and type-specific polymerase-chain-reaction-based methods. Cervical HPV infection was by far the most significant risk factor for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was greater for more severe lesions. The importance of the previously identified epidemiological risk factors for cervical neoplasia was also demonstrated. However, most of the effect of these factors could be explained by taking HPV infection into account, except for schooling and smoking. Non-use of barrier contraceptives and smoking were the only significant risk factors in HPV-positive women. In HPV-negative women, a residual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk determinants. Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infection increased to 80%. © 1996 Wiley-Liss, Inc.     

Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions

A systematic review was conducted of HPV type distribution in anal cancer and anal high‐grade and low‐grade squamous intraepithelial lesions (HSIL and LSIL). A Medline search of studies using PCR or hybrid capture for HPV DNA detection was completed. A total of 1,824 cases were included: 992 invasive anal cancers, 472 HSIL cases and 360 LSIL cases. Crude HPV prevalence in anal cancer, HSIL, and LSIL was 71, 91 and 88%, respectively. HPV16/18 prevalence was 72% in invasive anal cancer, 69% in HSIL and 27% in LSIL. The HPV 16 and/or 18 prevalence in invasive anal cancer cases was similar to that reported in invasive cervical cancer. If ongoing clinical trials show efficacy in preventing anal HPV infection and associated anal lesions, prophylactic HPV vaccines may play an important role for the primary prevention of these cancers in both genders. © 2008 Wiley‐Liss, Inc.     

The role of human papillomavirus in nongenital cancers

Answer questions and earn CME/CNE Human papillomavirus (HPV), one of the most common sexually transmitted diseases worldwide, has an established role in the pathogenesis of genital malignancies such as cervical cancer. The virus has also been implicated in the oncogenesis of nongenital cancers including head and neck malignancies (specifically oropharyngeal cancers) as well as anal cancer. There is less clarity regarding its role in lung and esophageal cancers. Worldwide, the incidence and prevalence of HPV‐associated oropharyngeal cancer has been increasing over time. These patients have improved outcomes compared with those with HPV‐negative oropharyngeal cancers, and there is continued interest in designing treatments specifically for this HPV‐positive subgroup. Clinicians continue to gain an understanding of HPV in anal cancers and the risk factors associated with infection and progression to malignancy. This has potential implications for the eventual screening of high‐risk groups. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has potential in the prevention of all HPV‐associated malignancies. In this review, current understanding of the role of HPV in nongenital cancers is discussed, as well as future implications for treatment and prevention. CA Cancer J Clin 2013. © 2012 American Cancer Society.