Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PURPOSE: To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. METHODS: The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. RESULTS: Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. RECOMMENDATIONS: In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended.It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis.

BACKGROUND: Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. METHODS: Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. FINDINGS: From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39-55 million) received the full course of vaccine, representing a total population coverage of 1·4% (95% CI 1·1-1·6), and 59 million women (48-71 million) had received at least one dose, representing a total population coverage of 1·7% (1·4-2·1). In more developed regions, 33·6% (95% CI 25·9-41·7) of females aged 10-20 years received the full course of vaccine, compared with only 2·7% (1·8-3·6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13·3 million vs 32·2 million). INTERPRETATION: Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention. FUNDING: PATH, Instituto de Salud Carlos III, and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR).

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Estimation of the potential overall impact of human papillomavirus vaccination on cervical cancer cases and deaths.

BACKGROUND: Human papillomavirus (HPV) vaccination offers potential for primary prevention of HPV-related pre-cancers and cancers as demonstrated in clinical trials. Mathematical models have estimated the potential real-life impact of vaccination on the burden of cervical cancer (CC). However, these are restricted to evaluations in a limited number of countries. METHODS: Potential decline in CC cases and deaths with the AS04-adjuvanted HPV-16/18 vaccine of young girls naïve to HPV, was estimated at steady-state (vaccine coverage: 0-100%) based on clinical trial and country-specific incidence data. Data on vaccine efficacy were taken from the end of study PATRICIA trial of the AS04-adjuvanted HPV-16/18 vaccine. The numbers of cases and deaths due to HPV-16/18 were estimated and compared with those due to any HPV type to estimate the additional cases prevented. This difference estimates CC cases and deaths avoided due to protection against non-vaccine HPV types. Cost-offsets due to reductions in CC treatment were estimated for five countries (Brazil, Canada, Italy, Malaysia and South African Republic) using country-specific unit cost data. Additionally, cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3)-related burden (cases and treatment costs) prevented by vaccination were estimated for two countries (Italy and Malaysia). RESULTS: HPV vaccination could prevent a substantial number of CC cases and deaths in countries worldwide, with associated cost-offsets due to reduced CC treatment. Cross-protection increased the estimated potential number of CC cases and deaths prevented by 34 and 18% in Africa and Oceania, respectively. Moreover, vaccination could result in a substantial reduction in the number of CIN2/3 lesions and associated costs. CONCLUSION: HPV vaccination could reduce the burden of CC and precancerous lesions in countries worldwide, part of disease burden reduction being related to protection against non HPV-16/18 related types.

Epidemiology and costs of screening and management of precancerous lesions of the cervix in Spain.

OBJECTIVE: Oncogenic human papillomaviruses (HPVs) are essential causes of cervical cancer. Screening prevents cancer by detecting precancerous lesions (cervical intraepithelial neoplasia, CIN). Our aim was to assess the annual number of Pap smears and CIN diagnoses in Spain and to estimate associated management costs. MATERIALS AND METHODS: A 1-year retrospective cross-sectional study was conducted among 65 gynecologists from public primary health care centers in 6 autonomous regions in Spain. We documented the total number of Pap smears performed and the management of women with CIN. Data on health care resource use related to CIN management for 2 years after diagnosis were collected and combined with unit costs to assess the mean cost per patient. We extrapolated to the general female Spanish population to estimate the total cost of screening and CIN management from the third-party payer's perspective. RESULTS: In our study sample, 3.5% of routine Pap smears were abnormal. We estimated that 7.6 million Pap smears are performed annually in Spain, at a cost of 622 million euro (US$987). Furthermore, 40,530 women are annually diagnosed with CIN 1, 26,243 with CIN 2, and 28,423 with CIN 3. The mean cost of CIN management per patient was 1,115 euro for CIN 1, 1,626 euro for CIN 2, and 2,090 euro for CIN 3. The total cost of CIN management was estimated at 147 million euro (US$233). CONCLUSIONS: This study shows that the costs of screening and management of CIN represent a heavy burden to the public health system in Spain.

Epidemiology and cost of treatment of genital warts in Spain.

BACKGROUND: Genital warts (GW) are common and increasing in young people. Ninety percent of GW are due to Human Papillomavirus (HPV) types 6 and 11. The objective of this study was to assess the epidemiology and management costs associated with GW in Spain. METHODS: A 1-year (2005) retrospective observational study was performed among a sample of gynaecologists, dermatologists and urologists in six autonomous regions in Spain. Men and women with newly diagnosed, recurrent or resistant GW were included. We estimated the incidence (new and recurrent cases) and prevalence (also including resistant cases) of GW. Healthcare resource use were collected and combined with unit costs to assess the mean cost of GW management per patient. These figures were extrapolated to the 14- to 64-year-old Spanish population to estimate the total cost of GW management from the Third Party Payer (TPP) and societal perspectives. RESULTS: The overall annual incidence of GW was estimated at 160.4 cases per 100,000. Overall prevalence was calculated as 182.1 cases per 100,000, corresponding to 56 446 GW cases annually (14- to 64-year-old population). The mean management cost was 833 euros and 1056 euro per patient from the TPP and societal perspective, respectively. The overall annual cost was estimated at 47 million euros and 59.6 million euros, from the TPP and societal perspective, respectively. CONCLUSION: This study provides a first overview of the burden of GW in Spain. A quadrivalent HPV vaccine that prevents HPV 6, 11, 16, 18 related diseases will have the potential to significantly decrease the socio-economic burden associated with GW in Spain.

Human papillomavirus vaccines and vaccine implementation.

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

Vaccine-related HPV genotypes in women with and without cervical cancer in Mozambique: burden and potential for prevention.

Knowledge about the burden of Human Papillomavirus (HPV) infections in Sub-Saharan Africa is very limited. We collected cervical samples from 262 women from the general population and 241 tumor samples from women with invasive cervical cancer in Mozambique and tested them for HPV genotyping by the SPF(10)-LiPA(25) PCR system. Among the 195 women without cervical abnormalities by cytology HPV prevalence was 75.9%. In this group of women, the most frequently identified HPV types among HPV-positive women were in descending order of frequency: HPV51 (23.6%), HPV35 (19.6%), HPV18 (14.2%), HPV31 (13.5%) and HPV52 (12.8%). In women with cervical cancer HPV DNA detection was 100%. The type-specific distribution of the most frequent types in descending order of frequency was: HPV16 (47.0%), HPV18 (31.3%), HPV51 (14.8%), HPV52 (14.3%), HPV45 (12.6%), HPV35 (10.4%), HPV33 (4.8%) and HPV31 (2.6%). HPVs 16/18 and HPVs 16/18/31/45 were detected in 71.7% and 80.9% of cervical cancer tissue, respectively. While HPVs 51 and 35 were the two most common types in cytologically normal women in Mozambique, HPVs 16 and 18 remained the two most frequently identified types in cervical cancer. The introduction of an efficacious HPV 16/18 vaccine could potentially prevent the occurrence of 72% of cervical cancer cases and up to 81% of the cases if full cross-protection against HPVs 31 and 45 is assumed.

Resource consumption and costs of palliative care services in Spain: a multicenter prospective study.

Patients (n=395) with terminal-stage cancer receiving attention from palliative care services (PCSs) were recruited over a period of 15 consecutive days from 171 participating PCS units. Resource consumption and costs were evaluated for 16 weeks of follow-up, and the findings were compared with a study conducted in 1992 so as to assess change over time. The most frequent health care interventions were homecare visits, hospital admissions, and patient-consultant phone calls. PCS provided 67% of all services and consultation interventions in 91% of patients. Compared with the historical data, there was a significant shift from the use of conventional hospital beds toward palliative care beds, a reduced hospital stay (25.5-19.2 days; P=0.002), an increase in the death-at-home option (31%-42%), a lower use of hospital emergency rooms (52%-30.6%; P=0.001), and an increase in programmed care. Compared to the previous resource consumption and expenditure study in 1992, the current PCS policy implies a cost saving of 61%, with greater efficiency and no compromise of patient care.