[Practice-relevant dietary recommendations in uro-oncology]. / Praxisrelevante Ernährungsempfehlungen in der Uroonkologie.

BACKGROUND: A healthy lifestyle is recommended for prevention, during therapy and in the survivorship of various medical conditions. OBJECTIVES: This article aims to give an overview of the current dietary recommendations and currently discussed topics which are useful for patient counseling. METHODS: The literature with a focus on uro-oncology, on prevention, during cancer therapy and survivorship was reviewed for healthy lifestyle recommendations. In addition, issues perceived in practice were researched, discussed with examples, and critically evaluated. RESULTS: The current recommendations of the professional associations are intended to encourage all healthy or already ill patients to adopt a healthy lifestyle that includes a balanced diet, physical activity and healthy body weight. Consistent with current evidence, neither general supplementation of dietary supplements nor avoidance of entire food groups (such as meat or dairy products) is recommended. CONCLUSIONS: In the counseling situation, patients should be encouraged in a healthy lifestyle or supported in an appropriate change of behavior. Any perceived uncertainty or questions from patient's perspective should be clarified and, if necessary, referred to a dietician, oecotrophologist or nutritionist.

Prophylactic gonadectomy in 46 XY females; why, where and when?

OBJECTIVES: We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy. CASE PRESENTATION: Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy. CONCLUSION: Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

Predictive Risk Factors for Continued Smoking after the Diagnosis of a Genitourinary Malignancy.

OBJECTIVE: To determine risk factors for continued smoking following a diagnosis of a genitourinary (GU) malignancy. Smoking is a well established risk factor in the development of cancers involving the GU tract. Unfortunately, a large percentage of patients continue to smoke or relapse after cancer diagnosis; by doing so, there is an increased risk of recurrence, poor survival rates, treatment complications, secondary primary cancers, and other chronic smoking related illnesses. MATERIALS AND METHODS: Two hundred and five patients who presented to a Urologic Oncology clinic at a single tertiary treatment center were given smoking cessation counseling and pharmacotherapy, as well as a questionnaire which was used to identify smoking status, demographics, and behavioral/psychosocial characteristics. Patients were followed for a minimum of 1 year with a median length of follow up for 13 months. RESULTS: 91% of patients enrolled in the study continued smoking at survey completion. After accounting for age, ethnicity, education and cigarettes consumed/day, 5 variables were independently associated with an increased risk of continued smoking: smoking 20 or more cigarettes per day, less than 2 prior quit attempts, anxiety and/or depression, fear of cancer recurrence, and home secondhand smoke exposure. CONCLUSION: The role of the urologist is imperative for encouraging smoking cessation. While every patient should receive adequate counseling regarding smoking at the time of a GU malignancy diagnosis, identifying patients with the risk factors noted in this study and augmenting smoking cessation efforts may result in stronger efforts to quit and prevention of long-term complications.

Recommandations françaises du Comité de cancérologie de l'AFU - actualisation 2020­2022: tumeurs de la voie excrétrice urinaire supérieure / French ccAFU guidelines - update 2020­2022: upper urinary tract urothelial carcinoma

The purpose was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC). A systematic Medline search was performed between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of UTUC, to evaluate different references with levels of evidence.The diagnosis of this rare pathology is based on CT-scan acquisition during excretion and ureteroscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment, nevertheless a conservative endoscopic approach can be proposed for low risk lesion: unifocal tumor, possible complete resection and low grade and absence of invasion on CT-scan. Close monitoring with endoscopic follow-up (flexible ureteroscopy) in compliant patients is therefore necessary. After RNU, bladder instillation of chemotherapy is recommended to reduce risk of bladder recurrence. A systemic chemotherapy is recommended after RNU in pT2­T4 N0­3 M0 disease. These updated guidelines will contribute to increase the level of urological care for diagnosis and treatment for UTUC.

L'objectif était de proposer une mise à jour des recommandations du Comité de cancérologie de l'Association française d'urologie (AFU) pour la prise en charge des tumeurs de la voie excrétrice supérieure (TVES). Une revue systématique de la littérature (Medline) a été effectuée de 2018 à 2020 sur les éléments du diagnostic, les options de traitement et la surveillance des TVES en évaluant les références avec leur niveau de preuve. Le diagnostic de cette pathologie rare repose sur l'uro-TDM avec acquisition au temps excréteur et l'urétérorénoscopie souple avec prélèvements biopsiques. Le traitement chirurgical de référence est la néphro-urétérectomie totale (NUT), mais un traitement conservateur peut être discuté pour les lésions dites « à bas risque ¼ : tumeur de bas grade, sans infiltration sur l'imagerie, unifocale < 2 cm, accessible à un traitement complet et nécessitant alors une surveillance endoscopique rapprochée par urétéroscopie souple chez un patient compliant. Une instillation postopératoire de chimiothérapie est recommandée et permet de diminuer le risque de récidive vésicale après NUT. La chimiothérapie adjuvante a démontré son bénéfice clinique comparée à la surveillance après NUT pour les tumeurs (pT2­T4 N0­3 M0). Ces nouvelles recommandations doivent contribuer à améliorer non seulement la prise en charge des patients, mais aussi le diagnostic et la décision thérapeutique des TVES.

Green tea (Camellia sinensis) for the prevention of cancer.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. OBJECTIVES: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. SEARCH METHODS: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. SELECTION CRITERIA: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. DATA COLLECTION AND ANALYSIS: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. MAIN RESULTS: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. AUTHORS' CONCLUSIONS: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.

A stepped-wedge cluster randomized trial designed to improve completion of HPV vaccine series and reduce missed opportunities to vaccinate in rural primary care practices.

OBJECTIVES: To test the effectiveness of a comprehensive team-based intervention to improve human papillomavirus (HPV) vaccination completion rates and reduce missed opportunities to vaccinate in rural Oregon. DESIGN: Stepped-wedge cluster randomized trial. PARTICIPANTS: Forty family physicians and pediatricians who are members of the Oregon Rural Practice-based Research Network. INTERVENTION: Tailored to individual practice needs, components will include (1) practice facilitation with clinicians, nurses, front office staff, and others who have patient contact to redesign patient care and communication strategies to optimize HPV vaccine series completion; (2) workflow mapping adapted to practice context to support HPV vaccine delivery; (3) a practice improvement model designed to firmly establish reminder and recall systems and then standing orders; (4) education for patients and parents that underscores HPV vaccination is safe, effective, and an important approach for reducing cancer risk; and (5) partnering with community organizations to plan and implement a social marketing campaign on HPV vaccination. MAIN OUTCOME MEASURES: Initiation and completion of the HPV vaccine series as well as reduction in rates of missed opportunities to vaccinate derived from Oregon Immunization Program data. TRIAL REGISTRATION: ClinicalTrials.govPRS, NCT03604393 : .Trial was registered on July 11, 2018. The first participant was enrolled on September 11, 2018.

Quality Improvement Initiative to Improve Human Papillomavirus Vaccine Initiation at 9 Years of Age.

OBJECTIVE: Adolescent human papillomavirus (HPV) vaccine rates remain low. Early vaccination may improve the efficacy of the vaccine and immunization rates; however, clinicians have not routinely made a strong recommendation for younger adolescents. This study assessed the feasibility of routine vaccination at 9 years of age. METHODS: Three sequential quality improvement (QI) interventions were implemented to shift the initiation of the HPV vaccine to 9 years of age in a primary care network in low-income neighborhoods in Columbus, Ohio. The first intervention changed the electronic medical record alert for the HPV vaccine from 11 to 9 years of age and focused on cancer prevention when discussing the vaccine with families. The second intervention was formation of an HPV QI team. The third intervention was a clinic incentive for HPV captured opportunity rates. Immunization rates were monitored using statistical process control charts to compare the HPV immunization rate in a sample of 9- and 10-year-old children with a sample of 11- and 12-year-old children. RESULTS: The percentage of patients receiving an HPV vaccine before 11 years increased from 4.6% to 35.7% during the 6 months after the QI initiative began and to 60.8% 18 months after the project began. In comparison, the HPV vaccination rate in the sample of 11- and 12-year-olds increased from 78.7% to 82.8% 18 months later. CONCLUSIONS: This QI project used multiple interventions to increase HPV vaccination at 9 years of age in a large primary care network serving a diverse low-income population.

[HPV vaccination]. / HPV-Impfung.

Human Papilloma Viruses are associated with genital carcinoma (of the cervix, anus, vulva, vagina and the penis) as well as with non-genital carcinoma (oropharyngeal carcinoma) and genital warts. In Switzerland two highly efficient and safe vaccines are available. The safety of these vaccines has been repeatedly subject of controversial discussions, however so far post marketing surveillance has always been able to confirm the safety. In Switzerland girls and young women have been offered the HPV vaccination within cantonal programmes since 2008. 2015 the recommendation for the HPV-vaccination for boys and young men was issued, and starting July 1, 2016 they as well will be offered vaccination free of charge within the cantonal programmes. This article discusses the burden of disease, efficacy and safety of the vaccines and presents facts which are important for vaccinating these young people. Specifically, aspects of the decisional capacity of adolescents to consent to the vaccination are presented. Finally, the future perspective with a focus on a new vaccine with an enlarged spectrum of HPV-types is discussed.

Lichen Sclerosus-Presentation, Diagnosis and Management.

BACKGROUND: Lichen sclerosus is a chronic inflammatory skin disease. It is thought to be underdiagnosed and undertreated. If it is not treated, lichen sclerosus is associated with a greater degree of scarring and an elevated risk of cancer in the genital area. METHODS: This review is based on pertinent articles published up to October 2015 that were retrieved by a selective search in PubMed, Embase, and the Cochrane Library and on the European S3 guideline for lichen sclerosus. RESULTS: Lichen sclerosus is mainly found in the anogenital area but can also be generalized. Extragenital involvement is reportedly present in 6% to 20% of patients. Neighboring mucous membranes, such as the vaginal or oral mucosa, are not typically affected. The disease is more common in women than in men, and occurs more often in adults than in children. About 10% of patients have other family members with the same condition. Anogenital lichen sclerosus often causes itching and pain. Functional impairment due to fissures and scars can arise over the course of the condition. The treatment of first choice is the local application of high-potency corticosteroids as early as possible (1/A). For boys and men in whom the condition does not remit after steroid treatment, circumcision is indicated (3/D). CONCLUSION: Anogenital itching and clinical features such as erythema, white skin changes (such as hyperkeratosis and sclerosis), and fissures should arouse suspicion of lichen sclerosus. The diagnosis should be confirmed with a skin biopsy, and early, thorough treatment should be initiated. In this way, a mutilating disease course can be averted, and the risk of cancer can be lessened.

[Genitourinary malignancies and rheumatoid arthritis]. / Urologische Malignome und rheumatoide Arthritis.

Genitourinary neoplasms are relatively common and the frequency increases with age. Due to demographic changes more patients with inflammatory rheumatic diseases will have concomitant genitourinary tumors or they will develop them under antirheumatic therapy. In such cases, disease-modifying antirheumatic drugs (DMARD) and immunosuppressive therapy have to be carefully balanced on an individual basis. Based on the limited evidence available large increases in the risks from conventional and/or biological DMARDs for patients with genitourinary malignancies appear to be unlikely for most situations. In addition to these more common situations paraneoplastic symptoms in the musculoskeletal system can occur due to genitourinary malignancies. Moreover, novel drugs with immunostimulating activity for some genitourinary tumors may provoke autoimmune symptoms and thus present new challenges for interdisciplinary cooperation between rheumatologists and uro-oncologists. In this review, the diagnostic procedures, therapies and follow-up of cancers in the field of urology are delineated according to the current German and European guidelines. We describe the core issues that both urologists and rheumatologists should bear in mind. Direct communication, routine exchange and involvement of rheumatologists in interdisciplinary tumor boards should improve future treatment quality of our joint patients.

HPV vaccination to prevent oropharyngeal carcinoma: What can be learned from anogenital vaccination programs?

Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy.

Uso del enfoque bayesiano para la estimación y proyección de tasas / Use of a bayesian approach to rate estimation and projection

OBJETIVO: Aplicar y valorar el enfoque bayesiano para realizar proyecciones de tasas de mortalidad por cáncer a través del ajuste de modelos edad-período-cohorte (EPC). MÉTODOS: El método de estimación bayesiano se aplica a datos de mortalidad por cáncer de vejiga en Argentina. Se adopta un esquema autorregresivo de segundo orden para la especificación a priori de los coeficientes del modelo EPC. Se comparan las estimaciones obtenidas con toda la información disponible y excluyendo los grupos de edad con tasas de mortalidad bajas, a fin de valorar el comportamiento del enfoque ante datos esparcidos. Se proyectan las tasas de mortalidad a dos períodos sucesivos a los observados. RESULTADOS: Se comprueba la robustez del método, lo cual evita excluir los grupos de edad con tasas de mortalidad nulas o bajas. Las tasas observadas caen todas dentro de las bandas de credibilidad y confirman la bondad del ajuste del modelo. Se observa una tendencia general decreciente de las tasas de mortalidad por cáncer de vejiga. Las estimaciones y proyecciones de estas tasas resultan más precisas en los grupos etarios que presentan mayor incidencia de mortalidad. CONCLUSIONES: La formulación bayesiana utilizada permite reducir la variación aleatoria entre estimaciones adyacentes al especificar que los efectos de cada escala dependan de los inmediatos anteriores. Se demuestra la capacidad del enfoque para manejar frecuencias bajas y obtener estimaciones confiables de las tasas de mortalidad, como así también proyecciones precisas sin necesidad de realizar supuestos adicionales como sucede en el ajuste clásico de un modelo EPC.

OBJECTIVE: Apply and assess a Bayesian approach to projecting cancer mortality rates by fitting age-period-cohort (APC) models. METHODS: The Bayesian estimation method was applied to bladder cancer mortality data in Argentina. A second-order autoregressive model was adopted for a priori specification of APC model coefficients. The estimates obtained were compared with all available information and excluding age groups with low mortality, to assess behavior of the approach in light of scattered data. Mortality was projected for two successive periods following the ones observed. RESULTS: Robustness of the method was verified, which avoids excluding age groups with null or low mortality. Observed rates all fall within the credibility bands and confirm the model's goodness of fit. An overall downward trend in bladder cancer mortality was observed. Estimates and projections of these rates are more precise in age groups that have greater incidence of mortality. CONCLUSIONS: The Bayesian formulation used herein makes it possible to reduce random variation between adjacent estimates by specifying that the effects of each scale depend on the immediately preceding ones. It was demonstrated that the approach has the capacity to handle low frequencies and obtain reliable mortality estimates, as well as precise projections, without the need for making additional assumptions, as happens in classical APC model fitting.

Committee Opinion Summary No. 641: Human Papillomavirus Vaccination.

Human papillomavirus (HPV) is associated with the development of anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. Human papillomavirus vaccination can significantly reduce the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only approximately one third of girls in the recommended age group have received all three vaccines. Compared with other vaccines recommended in the same age bracket, HPV vaccination rates in the United States are unacceptably low. It is crucial that obstetrician-gynecologists and other providers educate parents and patients on the benefits and safety of HPV vaccination. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine vaccination with HPV vaccine for girls and boys. The 9-valent HPV vaccine is recommended by the Advisory Committee on Immunization Practices and was licensed by the U.S. Food and Drug Administration in December 2014 for girls and boys aged 11-12 years.

Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys.

BACKGROUND: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. METHODS: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. RESULTS: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. CONCLUSIONS: At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.

Green tea polyphenols and cancer chemoprevention of genitourinary cancer.

Green tea, which has higher concentrations of polyphenols than other teas, has been correlated with reduced risk of various malignancies with most data supporting a potential protective role in prostate neoplasia. Preclinical studies over the last 25 years implicate constituent green tea catechins, epigallocatechin-3-gallate (EGCG) being the predominant form, as the main mechanistic ingredient in the observed biologic effects, which vary from proapoptotic effects to inhibition of androgen receptor and signal transduction pathways. There have been few prospective clinical trials of green tea polyphenols (GTP), especially with well-characterized formulations and doses. Although there have been hints of beneficial clinical activity in prostate neoplasia, other studies have raised concerns about the limited bioavailability and very low target-tissue concentrations of GTPs. At present there is no proven role for GTP supplementation in the prevention of genitourinary (GU) malignancies, but novel GTP formulations and further clinical testing may still support a future for GTP supplementation in GU cancer prevention.

Emerging human papillomavirus vaccines.

INTRODUCTION: Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. AREAS COVERED: Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. EXPERT OPINION: Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies.