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Cancer Statistics
Population in 2008: 9.7m
People newly diagnosed with cancer (excluding NMSC) / yr: 8,700
Age-standardised rate, incidence per 100,000 people/yr: 121.6
Risk of getting cancer before age 75:12.6%
People dying from cancer /yr: 5,200
Data from IARC GlobalCan (2008)
Bolivia: Cancer Organisations and Resources
Latest Research Publications from Bolivia

Bolivia: Cancer Organisations and Resources (4 links)

Latest Research Publications from Bolivia

Hsieh R, Nico MM, Camillo CM, et al.
Mutational Status of NRAS and BRAF Genes and Protein Expression Analysis in a Series of Primary Oral Mucosal Melanoma.
Am J Dermatopathol. 2017; 39(2):104-110 [PubMed] Related Publications
Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma. The aim of this study was to evaluate NRAS and BRAF genes, both components of mitogen-activated protein kinase molecular pathway, and compare with their protein expression. Point mutations of NRAS (codons 12, 13, and 61) and BRAF (codon 600) were screened by pyrosequencing method, and its results were associated to the protein expression of RAS and BRAF performed by immunohistochemistry. The authors observed mutation in BRAF 600 (3/14), NRAS codons 12 and 13 (2/14), and NRAS codon 61 (2/8). One case showed positive RAS protein expression, but no mutation was observed. Twelve in 14 cases showed positive BRAF protein expression: 3 cases showed BRAF mutation; 2 cases showed NRAS codon 61 mutation; 2 cases showed NRAS codons 12 and 13 mutation but not simultaneously. Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.

Sakai K, Loza E, Roig GV, et al.
CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians.
Asian Pac J Cancer Prev. 2016; 17(2):781-4 [PubMed] Related Publications
The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

Castellsagué X, Alemany L, Quer M, et al.
HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.
J Natl Cancer Inst. 2016; 108(6):djv403 [PubMed] Related Publications
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.

Plaza JA, Bonneau P, Prieto V, et al.
Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis.
J Cutan Pathol. 2016; 43(4):313-23 [PubMed] Related Publications
Desmoplastic melanoma (DM) is histologically characterized by a proliferation of spindle melanocytes dispersed in a collagenous stroma that can be mistaken for a variety of neoplasms. The purpose of this study was to analyze 40 cases of DM with a comprehensive panel of immunohistochemical markers (KBA.62, p16, Ezrin, WT-1, MITF-1, SOX-10, CD117, SOX-2, nestin, PNL2, p75, MART-1, gp100 and S100p) to obtain a more complete understanding of the potential use of these antibodies in the diagnosis of DM. We found that all cases of DM expressed p16, WT-1, SOX-10, nestin and S100p and 95% of cases expressed p75. There was variable expression with Ezrin, SOX-2, KBA.62, MART-1 and HMB-45. Most DMs did not express MITF-1, PNL2 and CD117. Conditions that may enter in the histologic differential diagnosis of DM, including dermal scars, fibromatosis and dermatofibromas were also studied. Nearly all control cases also stained positive for p16 but were negative for WT1, SOX10, nestin, p75 and S-100p, as well as for most of the other markers tested. We conclude that a panel of S-100p, WT1, SOX10, p75 and nestin may constitute the optimal panel with the most sensitive and specific combination of immunostain available for the diagnosis of DM.

Fernandes JD, Hsieh R, de Freitas LA, et al.
MAP Kinase Pathways: Molecular Roads to Primary Acral Lentiginous Melanoma.
Am J Dermatopathol. 2015; 37(12):892-7 [PubMed] Free Access to Full Article Related Publications
The etiology and pathogenesis of lentiginous acral melanomas are poorly understood. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma, particularly changes in the MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2). The aim of this study is to assess the status of the MAP kinase pathways in the pathogenesis of acral melanomas. The authors examined the components of the RAS-RAF-MEK-ERK cascades by immunohistochemistry in a series of 16 primary acral melanomas by tissue microarray. The expression of MAP kinase cascade proteins changed in most cases. The authors observed that 57.14% of cases were BRAF positive and that 61.53%, 71.42%, and 71.42% of cases were positive for MEK2, ERK1, and ERK2, respectively; RAS was not expressed in 92.31%, and all cases were negative for MEK1. The absence of RAS and positivity for MEK2, ERK1, and ERK2 were most seen in invasive cases with high thickness. These aspects of the MAPK pathway require further examination in acral melanomas between different populations. Nevertheless, the results highlight significant alterations in the MAP kinase cascades that are related to histological indicators of prognosis in primary acral melanomas.

Plaza JA, Mackinnon A, Carrillo L, et al.
Role of immunohistochemistry in the diagnosis of sebaceous carcinoma: a clinicopathologic and immunohistochemical study.
Am J Dermatopathol. 2015; 37(11):809-21 [PubMed] Related Publications
Sebaceous carcinoma (SC) is a relatively uncommon malignant epithelial neoplasm with a predilection for the periocular region. The diagnosis of SC can be difficult to make at initial presentation, as it can clinically and histopathologically resemble other common benign and malignant epithelial lesions. A diagnosis of SC is made by confirmation of sebaceous differentiation of neoplastic cells, which can often be accomplished by conventional microscopic findings; however, its recognition may be sometimes difficult and requires ancillary studies such as immunohistochemistry (IHC). Many studies have evaluated the role of IHC as a potential technique to differentiate SC from its mimics; however, most of these studies have used a limited panel of antibodies with variable results. The aim of this study was to determine the efficacy of IHC in the diagnosis of SC and to provide some guidelines for interpretation in the diagnosis of these neoplasms. We studied 27 cases of SC with a broad panel of IHC markers using a tissue microarray technique. We also studied 21 control cases of basal cell carcinoma (BCC) and 22 control cases of squamous cell carcinoma (SCC). Representative tissue cores were taken and processed from each case, and the tissue microarrays were stained by standard methods using antibodies to EMA, CK7, Ber-EP4, Factor XIIIA, androgen receptor, p53, adipophilin, progesterone receptor membrane component 1 (PGRMC1), squalene synthase (SQS), and alpha/beta hydrolase domain-containing protein 5 (ABHD5). Our studies show that EMA was expressed in all cases of SC, CK7 was expressed in 24 of 27 cases, Ber-EP4 was expressed in 7 of 27 cases, Factor XIIIA was negative in all cases, androgen receptor was expressed in 9 of 27 cases, P53 was expressed in 12 of 27 cases, adipophilin was expressed in all cases, PGRMC1 was expressed in 22 of 27 cases, SQS was expressed in 11 of 27 cases, and ABHD5 was expressed in 9 of 27 cases. EMA was negative in all cases of BCC, CK7 was expressed in 6 of 21 cases, Ber-EP4 was expressed in 21 of 21 cases, Factor XIIIA was negative in all cases, androgen receptor was expressed in 3 of 21 cases, P53 was expressed in 4 of 21 cases, adipophilin, PGRMC1, SQS, and ABHD5 were negative in all cases of BCC. Similarly, EMA was expressed in 16 of 22 cases of SCC, CK7 was expressed in 2 of 22 cases, Ber-EP4, Factor XIIIA, and androgen receptor were negative in all cases, P53 was expressed in 3 of 22 cases, adipophilin, PGRMC1, SQS, and ABHD5 were negative in all cases of SCC. Our study indicates that adipophilin represents a sensitive and reliable marker for the diagnosis of SC and can be of help in separating this tumor from some of its mimics. Additionally, inclusion of various epithelial markers in the panel will be of help if adequately used. Other antibodies against the PAT family of lipid droplet-associated proteins including PGRMC1, SQS, and ABHD5 were not as sensitive as adipophilin for identifying sebaceous differentiation and may therefore not be as useful for differential diagnosis as adipophilin.

Ikoma T, Tsuchiya Y, Asai T, et al.
Ochratoxin A Contamination of Red Chili Peppers from Chile, Bolivia and Peru, Countries with a High Incidence of Gallbladder Cancer.
Asian Pac J Cancer Prev. 2015; 16(14):5987-91 [PubMed] Related Publications
Our previous study detected aflatoxins in red chili peppers from Chile, Bolivia, and Peru, each of which have a high incidence of gallbladder cancer (GBC). Since the aflatoxin B1 concentration was not so high in these peppers, it is important to clarify the presence of other mycotoxins. Here we attempted to determine any associations between the concentrations of aflatoxins and ochratoxin A (OTA) in red chili peppers, and the corresponding GBC incidences. We collected red chili peppers from three areas in Peru: Trujillo (a high GBC incidence area), Cusco (an intermediate GBC incidence area), and Lima (a low GBC incidence rate), and from Chile and Bolivia. Aflatoxins and OTA were extracted with organic solvents. The concentrations of aflatoxins B1, B2, G1, and G2, and OTA were measured by high-performance liquid chromatography. The values obtained were compared with the incidence of GBC in each area or country. All of the red chili peppers from the three areas showed contamination with aflatoxins below the Commission of the European Communities (EC) recommended limits (5 μg/kg), but the OTA contamination of two samples was above the EC recommended limit (15 μg/kg). The mean concentrations of OTA in the peppers from Chile (mean 355 μg/kg, range <5-1,059 μg/kg) and Bolivia (mean 207 μg/kg, range 0.8-628 μg/kg), which has a high incidence of GBC, were higher than that in Peru (14 μg/kg, range <5-47 μg/kg), which has an intermediate GBC incidence. The OTA contamination in the red chili peppers from Chile, Bolivia, and Peru was stronger than that of aflatoxins. Our data suggest that OTA in red chili peppers may be associated with the development of GBC.

Harding-Jackson N, Sangueza M, Mackinnon A, et al.
Spindle Cell Atypical Fibroxanthoma: Myofibroblastic Differentiation Represents a Diagnostic Pitfall in This Variant of AFX.
Am J Dermatopathol. 2015; 37(7):509-14; quiz 515-6 [PubMed] Related Publications
Atypical fibroxanthoma (AFX) is a low-grade, dermal, mesenchymal neoplasm, which lacks a specific lineage of differentiation. The classical histologic appearance of AFX is that of a pleomorphic and spindle cell neoplasm with marked nuclear pleomorphism, mitotic figures, and often prominent storiform pattern that superficially resembles a pleomorphic high-grade sarcoma ("malignant fibrous histiocytoma"). Many histologic variants have been described. We have reviewed 15 cases of AFX characterized by a pure spindle cell morphology that could be easily mistaken for other spindle cell dermal neoplasms. All of our cases were stained with CD68, CD163, CD10, S-100p, p63, wide-spectrum keratin, CD31, CD34, smooth muscle actin (SMA), desmin, calponin, and h-caldesmon. All 15 cases showed an immunoprofile consistent with AFX. In 9 cases, SMA was also strongly expressed; this finding, coupled with the malignant spindle cell histomorphology, can lead to an erroneous diagnosis of cutaneous leiomyosarcoma with potential clinical consequences. Awareness of this pattern of immunoreactivity in this unusual variant of AFX is of importance for avoiding diagnostic misinterpretation. This study intends to characterize the nature and frequency of SMA immunoreactivity in AFX and to discuss the potential diagnostic pitfalls of immunohistochemical markers in distinguishing this entity from other malignant spindle cell neoplasms.

Pichon-Riviere A, Garay OU, Augustovski F, et al.
Int J Technol Assess Health Care. 2015; 31(1-2):2-11 [PubMed] Related Publications
OBJECTIVES: Differential pricing, based on countries' purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA).
METHODS: A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country.
RESULTS: Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA.
CONCLUSIONS: Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

zur Hausen H, de Villiers EM
Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers.
Int J Cancer. 2015; 137(4):959-67 [PubMed] Related Publications
The analysis of published epidemiological data on colon and breast cancer reveals a remarkable concordance for most regions of the world. A low incidence for both cancers has been recorded in Mongolia and Bolivia. Discrepant data, however, have been reported for India, Japan and Korea. In India, the incidence of breast cancer is significantly higher than for colon cancer, in Japan and Korea colon cancer exceeds by far the rate of breast cancer. Here, studies are summarized pointing to a species-specific risk for colon cancer after consumption of beef originating from dairy cattle. Uptake of dairy products of Bos taurus-derived milk cattle, particularly consumed at early age, is suggested to represent one of the main risk factors for the development of breast cancer. A recent demonstration of reduced breast cancer rates in individuals with lactose intolerance (Ji et al., Br J Cancer 2014; 112:149-52) seems to be in line with this interpretation. Species-specific risk factors for these cancers are compatible with the transmission of different infectious factors transferred via meat or dairy products. Countries with discordant rates of colon and breast cancer reveal a similar discordance between meat and milk product consumption of dairy cattle. The recent isolation of a larger number of novel presumably viral DNAs from serum, meat and dairy products of healthy dairy cows, at least part of them infectious for human cells, deserves further investigation. Systemic infections early in life, resulting in latency and prevention of subsequent infections with the same agent by neutralizing antibodies, would require reconsideration of ongoing prospective studies conducted in the adult population.

Plaza JA, Sangueza M
Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.
Am J Dermatopathol. 2015; 37(1):20-5 [PubMed] Related Publications
Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Sanchez PC, Noda AY, Franco DD, et al.
Melanoma in children, adolescents, and young adults: a clinical pathological study in a Brazilian population.
Am J Dermatopathol. 2014; 36(8):620-8 [PubMed] Related Publications
Malignant melanoma in children, adolescents, and young adults is unusual, especially before puberty. In children (age, 0-14 years), most primary lesions are thick and atypical (amelanotic, simulating pyogenic granuloma). In the population of adolescents and young adults (age, 15-39 years), melanoma is the third most common cancer, only behind lymphoma and breast cancer. Our study investigated the records of 89 patients diagnosed with cutaneous melanoma at age 0-39 years at Hospital das Clínicas, Medical School, University of São Paulo between 1992 and 2002. They were divided into group A (0-14 years of age) and group B (15-39 years of age). The histopathology of all cases was reexamined. Statistical analysis of the data presented was performed, and the obtained data were compared with the literature. The frequency of melanoma in the group aged 15-39 years was higher in women, and the most affected site was the trunk. Additionally, melanomas were more frequent at an earlier age in patients with family history of melanoma (P = 0.014). Most cases were diagnosed, at histopathology, as superficial spreading melanoma. Thick nodular melanomas with Breslow values higher than 2 mm were associated with lymph node metastasis (P < 0.05). Our study revealed that melanoma in children, adolescents, and young adults may present peculiar behavior and outcome, which might reflect the genetic and yet not fully unraveled pathogenesis of this complex disease.

Asai T, Loza E, Roig GV, et al.
High frequency of TP53 but not K-ras gene mutations in Bolivian patients with gallbladder cancer.
Asian Pac J Cancer Prev. 2014; 15(13):5449-54 [PubMed] Related Publications
Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.

Sivapalasingam S, Rajasingham A, Macy JT, et al.
Recurrence of Helicobacter pylori infection in Bolivian children and adults after a population-based "screen and treat" strategy.
Helicobacter. 2014; 19(5):343-8 [PubMed] Related Publications
BACKGROUND: Strategies to prevent gastric cancer by decreasing Helicobacter pylori infections in high-prevalence, low-income countries could include a population-based "screen and treat" eradication program.
METHODS: We tested residents of two rural villages for H. pylori infection using urea breath test (UBT), treated infected persons using directly observed therapy (DOT), retested for cure, and retested after 1 year later for H. pylori infection.
FINDINGS: We tested 1,065 (92%) of 1153 residents from two villages in rural Bolivia. Baseline H. pylori prevalence was 80% (95% confidence interval [CI]: 78-84). Age-specific cure rates were similar (≥92%) after DOT. Among those cured, 12% (95% CI: 8-15) had recurrent infection. Age-specific annual H. pylori recurrence rates for combined villages were 20% (95% CI: 10-29) in persons <5 years, 20% (95% CI: 10-29) in 5-9 years, 8% (95% CI: 1-15) in 10-14 years, and 8% (95% CI: 4-12) in persons ≥15 years. Compared with the referent population, those ≥15 years, recurrent infections were significantly more likely in children <5 years (odds ratios [OR] 2.7, 95% CI: 1.2-5.8) and 5-9 years (OR 2.7, 95% CI: 1.4-5.1).
INTERPRETATION: Children <10 years had high H. pylori recurrence rates following a population-based screen and treat program; this H. pylori eradication strategy may not be feasible in high-prevalence, low-income settings.

Plaza JA, De Stefano D, Suster S, et al.
Intradermal spitz nevi: a rare subtype of spitz nevi analyzed in a clinicopathologic study of 74 cases.
Am J Dermatopathol. 2014; 36(4):283-94; quiz 295-7 [PubMed] Related Publications
Spitz nevi are acquired melanocytic lesions with a wide histomorphological spectrum; reliable distinction from spitzoid melanoma is often difficult. Misdiagnoses of benign spitzoid tumors as spitzoid melanomas and vice versa are attributable to a frequently disturbing morphology and inconsistent or poorly defined histological criteria for diagnosis. Many recognized histological variants of Spitz nevi have been described, including the intradermal Spitz. Histopathologic descriptions of intradermal Spitz nevi have been done in the past; however, large studies addressing their histological spectrum have been lacking. We have retrospectively assessed the morphological features in 74 cases of intradermal Spitz nevi, excluding tumors clearly defined as atypical Spitz nevi and Spitzoid melanomas, to further delineate their histological spectrum. The patients' ages ranged from 5 to 81 years (median: 27). Anatomic location included: the upper extremities (27 cases), followed by head and neck (22 cases), lower extremities (9 cases), back (8 cases), buttock (5 cases), chest (1 case), and vulva (1 case). In 1 case, the anatomic location of the lesion was not available. Different histological variants were observed including hyalinized, polypoid, desmoplastic, angiomatoid, and halo Spitz. Morphological features evaluated included symmetry (100%), cell type (epithelioid 42%, spindle 16%, mixed 42%), maturation (85%), pigmentation (26%), chronic inflammation (24%), and mitotic activity (38%). Mild atypia was seen in 36 cases (49%), moderate atypia was seen in 28 cases (38%), and severe atypia was seen in 10 cases (14%). Intradermal Spitz nevus is a distinctive type of Spitz nevus that sometimes can be difficult to define given the unusual features that these lesions can show; thus, strict application of well-defined histological criteria and awareness of their morphological spectrum will facilitate definitive diagnosis.

Plaza JA, Requena L, Kazakov DV, et al.
Verrucous localized lymphedema of genital areas: clinicopathologic report of 18 cases of this rare entity.
J Am Acad Dermatol. 2014; 71(2):320-6 [PubMed] Related Publications
BACKGROUND: Localized lymphedema is a nonneoplastic condition associated with obesity and predominantly involving the legs. This condition has distinctive clinical and histologic features and only rarely has been mentioned in the dermatologic literature.
OBJECTIVE: We sought to evaluate the clinical and histopathologic features.
METHODS: The clinicopathologic features in patients with localized lymphedema of the genital region were studied.
RESULTS: We identified 18 patients with localized lymphedema clinically presenting as large polypoid or verrucous lesions. The patients were 5 men and 13 women with a mean age of 46.5 years. Twelve patients were obese at diagnosis. Thirteen patients presented with tumors involving the vulva, 4 patients with tumors in the penis and scrotum, and 1 patient with scrotal and pubic lesions. Histologically, all cases showed marked dermal edema along with dilated lymphatic spaces, fibroplasia, and verrucous epidermal changes (papillomatous and hyperplastic epidermis).
LIMITATIONS: Only 18 cases were included in our study.
CONCLUSIONS: This condition is an uncommon and recently described entity that could potentially be clinically and histologically misdiagnosed as a neoplasm; thus, it needs to be included in the differential diagnosis of polypoid and verrucous skin tumors with extensive dermal edema and fibroplasia.

Plaza JA, Kacerovska D, Sangueza M, et al.
Can cutaneous low-grade B-cell lymphoma transform into primary cutaneous diffuse large B-cell lymphoma? An immunohistochemical study of 82 cases.
Am J Dermatopathol. 2014; 36(6):478-82 [PubMed] Related Publications
Low-grade B-cell lymphomas of the skin, especially, primary cutaneous follicle center cell lymphoma has several distinctive features when compared with nodal/systemic follicular lymphomas, as they are frequently negative for bcl-2 and CD10, and only fewer than 25% of the cases show a bcl-2 rearrangement. The risk of transformation of a cutaneous low-grade B-cell lymphoma, such as primary cutaneous follicle center cell lymphoma, to primary cutaneous diffuse large B-cell lymphomas (PCDLBCL) has not been clearly delineated in the literature. Transformation of systemic/nodal follicular lymphoma into aggressive DLBCL is associated with rapid disease progression, refractoriness to treatment, and poor prognosis. The authors studied 82 cases of primary cutaneous DLBCL using antibodies for follicular dendritic cells (FDCs), CD21, and CD35 to detect networks of FDCs that could possibly indicate transformation of preexisting low-grade B-cell lymphoma to PCDLBCL. All cases were classified as PCDLBCL using strict histologic and immunophenotypic criteria. Fifty-three cases were classified as primary cutaneous DLBCL of "leg type," and 29 cases were classified as primary cutaneous DLBCL, "NOS" category. Immunohistochemical studies were performed in all 82 cases; in 15 cases, a CD21/CD35+ network of FDCs was noted within the tumor, indicating the presence of remnants of residual germinal centers, suggesting the possibility of a transformed low-grade B-cell lymphoma. In summary, the authors' findings seem to indicate that some cases of primary cutaneous DLBCL may result from transformation of a low-grade B-cell lymphoma. Further studies are necessary to evaluate the significance of their findings by using ancillary techniques including genetic analysis.

Plaza JA, Kazakov DV, Casas G, et al.
Fibrolipomatous hamartoma of the nerve: a clinicopathologic report of 13 cases.
J Am Acad Dermatol. 2014; 70(4):736-42 [PubMed] Related Publications
BACKGROUND: Fibrolipomatous hamartoma of the nerve is a rare benign infiltrating condition of peripheral nerves with prominent cutaneous findings that has not being well described in the dermatologic and dermatopathologic literature.
OBJECTIVE: We sought to evaluate the clinical and histopathological features of this rare condition.
METHODS: We reviewed the clinicopathologic features of 13 cases to delineate their clinical presentation and histopathologic spectrum.
RESULTS: All patients presented with unilateral lesions on the thenar areas, fingers, or both. In 7 cases the lesions presented congenitally and in 6 cases the lesions presented sporadically. Histologically, we found 2 patterns that have only been rarely mentioned before including cases with intraneural perineurioma-like features and cases with marked nerve hyperplasia.
LIMITATIONS: Only 13 cases were included in our study.
CONCLUSIONS: This condition is an uncommon entity. The diagnosis of this disorder can be highly suspected on its macroscopic features. Predilection of the median nerve and the frequent association with macrodactyly are characteristic clinical findings.

Dabdoub CB, Dabdoub CF, Chavez M, et al.
Abdominal cerebrospinal fluid pseudocyst: a comparative analysis between children and adults.
Childs Nerv Syst. 2014; 30(4):579-89 [PubMed] Related Publications
PURPOSE: Abdominal cerebrospinal fluid (CSF) pseudocyst is a rare but important complication in patients with ventriculoperitoneal shunt (VPS). In addition to presenting our experience, we performed a comparative analysis between children and adults with this entity. To the author's knowledge, there are no studies in which this condition has been compared.
METHODS: The PubMed database was searched for all relevant reports published from 1954 to 2012. The differences were statistically compared, especially regarding clinical investigations, etiology of the hydrocephalus, shunt revision, CSF infection, treatment, and recurrence. Chi-square test or Fisher's exact test was used to find associations among the variables.
RESULTS: Compiled from literature, we found 393 cases of abdominal pseudocyst: 295 children, including our cases, and 55 adults, with age not informed in 43 cases. In children, 33 % of the patients have a positive culture on presentation, with higher incidence in children younger than 10 years. In contrast, only 15 % among adults were positive CSF culture. In total, 287 abdominal pseudocyst cases who underwent shunt revision have been reported; 78.4 % of children and 62.2 % of adults. The main occurrence of this complication according to the etiology of hydrocephalus in children was different from adults. The recurrence of pseudocyst occurred in 19.8 and 24.2 % of children and adults, respectively.
CONCLUSIONS: The differences between children and adults might represent distinct trends on the etiology and treatment of this entity. Hence, additional well-designed cohort studies will be necessary to strengthen our findings.

Lourenço SV, Fernandes JD, Hsieh R, et al.
Head and neck mucosal melanoma: a review.
Am J Dermatopathol. 2014; 36(7):578-87 [PubMed] Related Publications
Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis.

Moore SP, Forman D, Piñeros M, et al.
Cancer in indigenous people in Latin America and the Caribbean: a review.
Cancer Med. 2014; 3(1):70-80 [PubMed] Free Access to Full Article Related Publications
Cancer is a leading cause of death in Latin America but there have been few assessments of the cancer burden for the 10% of the population who are indigenous. Evidence from other world regions suggests cancer survival is poorer for indigenous people than for others due to a greater incidence of case-fatal cancers, later stage at diagnosis, and less cancer treatment. A status report on the cancer profile of indigenous people in Latin America and the Caribbean (LAC) is therefore clearly warranted. We undertook a systematic review of the peer-reviewed literature in academic databases, and considered evidence from cancer registries from 1980, to assess cancer epidemiology among indigenous people in LAC. We identified 35 peer-reviewed articles pertaining to cancer in indigenous people. Rates of cervical cancer in parts of Brazil, Ecuador, and Guyana, stomach cancer rates in regions of Chile and gallbladder rates in Chile and Bolivia, were higher for indigenous compared to others. Breast cancer rates were lower in Ecuador, Brazil, and Chile. Six cancer registries in Brazil provided incidence data but no other reports of incidence, mortality, or survival were identified. There was a paucity of data surrounding the cancer burden of indigenous people in LAC. In view of predicted increases in cancer rates in ensuing decades, and the disparities in burden already experienced by indigenous people in the region, it is imperative that cancer profiles are obtained and cancer control measures identified and prioritized.

Gold KA, Kim ES, Liu DD, et al.
Prediction of survival in resected non-small cell lung cancer using a protein expression-based risk model: implications for personalized chemoprevention and therapy.
Clin Cancer Res. 2014; 20(7):1946-54 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers.
EXPERIMENTAL DESIGN: We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS).
RESULTS: A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phospho-adenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P < 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P < 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure-specific endonuclease-1 predicted unfavorable OS.
CONCLUSION: We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC.

Stormo AR, Espey D, Glenn J, et al.
Findings and lessons learned from a multi-partner collaboration to increase cervical cancer prevention efforts in Bolivia.
Rural Remote Health. 2013 Oct-Dec; 13(4):2595 [PubMed] Related Publications
Cervical cancer is a leading cause of cancer death among women in Bolivia, where cytology based screening has not performed well due to health-systems constraints. In response, the Centers for Disease Control and Prevention and the Pan American Health Organization partnered with the Bolivian Ministry of Health and the Peruvian Cancer Institute (INEN) to build capacity in Bolivia for the use of visual inspection of the cervix with acetic acid (VIA) and cryotherapy. Four 5-day courses on basic clinical skills to perform these procedures, provide related counseling, and manage side effects and infections were conducted from September 2010 to December 2012 for 61 Bolivian nurses and physicians. Of these courses, two were conducted by Bolivian trainers that were certified through a Training-of-Trainers course taught by the INEN. Classroom didactic sessions included lectures and practice with anatomic models followed by clinical practice sessions to provide trainees with practical experience in VIA and cryotherapy. Pre- and post-training evaluations were administered to ascertain knowledge gained. Evaluation of competency was conducted during simulation exercises in the classroom and during supervised performances of procedures in clinical settings. This report summarizes findings and lessons learned that will be useful for planning the supervision and monitoring phase of this project as well as for future partnerships in the Latin American and the Caribbean region.

Chang J, Prieto VG, Sangueza M, Plaza JA
Diagnostic utility of p63 expression in the differential diagnosis of pagetoid squamous cell carcinoma in situ and extramammary Paget disease: a histopathologic study of 70 cases.
Am J Dermatopathol. 2014; 36(1):49-53 [PubMed] Related Publications
Pagetoid squamous cell carcinoma in situ (PSCCIS) is characterized by cytologically atypical cells, with abundant, pale-staining cytoplasm arranged singly and in nests within the epidermis (pagetoid distribution). The growth pattern of PSCCIS may simulate extramammary Paget disease (EMPD), and in some cases, it is difficult to differentiate the 2 entities based on histomorphology alone. In this study, biopsy samples from 30 cases of PSCCIS and 40 cases of primary EMPD were examined using immunohistochemical staining for p63. In cases where the boundaries between the pagetoid cells and surrounding keratinocytes were difficult to assess, an eosin counterstain was applied to highlight the cytoplasm of the lesional cells. The immunohistochemical results were analyzed using Fisher exact test. The results showed that all 30 cases of PSCCIS exhibited strong nuclear positivity for p63 in the neoplastic cells, when compared with 0 of 40 cases of primary EMPD (P < 0.0001). In summary, p63 is a useful marker in differentiating PSCCIS from primary EMPD. The authors propose the addition of p63 immunostain in the panel of markers when evaluating pagetoid cutaneous neoplasms.

Bologna SB, Nico MM, Hsieh R, et al.
Adhesion molecules in primary oral mucosal melanoma: study of claudins, integrins and immunoglobulins in a series of 35 cases.
Am J Dermatopathol. 2013; 35(5):541-54 [PubMed] Related Publications
Primary oral mucosal melanoma is a rare aggressive tumor. Recent studies have demonstrated a correlation between increased tumor invasion and the metastatic phenotype and altered adhesion molecule expression profiles. The present study analyzed the expression of integrins, claudins, and immunoglobulin-like adhesion molecules in oral mucosal melanomas and correlated results with clinical parameters. Immunohistochemical analyses of the expression patterns of these molecules were performed on thirty-five cases of primary oral mucosal melanomas organized in a tissue microarray. The results were correlated with clinical and histological features of the cohort. A number of integrin subunits were negative and this was related with vascular invasion. Positivity of integrin beta-3 and CD166 (activated leukocyte cell adhesion molecule) was statistically associated with extensive vascular invasion (P < 0.05). Lower expression of CD54 (intercellular cell adhesion molecule) was associated with cases with extensive necrosis. Most cases with metastatic disease were negative for CD66 (carcinoembryonic antigen-related cell adhesion molecule). Several subunits of claudins were negative and, although not statistically significant, this lack of expression was partially associated with histological factors of poor prognosis. Altered patterns of adhesion molecule expression, mainly integrins and immunoglobulin-like proteins, may participate in the pathogenesis and outcome of oral mucosal melanomas.

Soneji S, Fukui N
Socioeconomic determinants of cervical cancer screening in Latin America.
Rev Panam Salud Publica. 2013; 33(3):174-82 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To assess the impact of health care access and socioeconomic determinants on Pap smear screening in Latin America.
METHODS: Individual-level data was collected from the Demographic and Health Surveys in Bolivia, Brazil, Dominican Republic, Ecuador, Guatemala, Nicaragua, Peru, and Trinidad and Tobago between 1987 and 2008. Multivariate logistic regression analyses were used to identify socioeconomic and health care determinants of two outcomes: knowledge of Pap smears and recent Pap smear screening.
RESULTS: In all countries, the proportion of women with a recent Pap smear screening remained below 55%. Key determinants of knowledge of Pap smears were age, education, and recent doctor's visit. For recent Pap smear screening, key determinants were wealth and recent doctor's visit. Women were between 1.47 and 3.44 times more likely to have received a recent Pap smear if they had a recent doctor's visit. Even the poorest women with a recent doctor's visit were more likely to screen than the richest women without a recent visit.
CONCLUSIONS: These data suggest that visiting a doctor is an important determinant of cervical cancer screening in Latin America. Because screening may coincide with other medical visits, physicians could effectively encourage screening.

Sangueza M, Plaza JA
Hydroa vacciniforme-like cutaneous T-cell lymphoma: clinicopathologic and immunohistochemical study of 12 cases.
J Am Acad Dermatol. 2013; 69(1):112-9 [PubMed] Related Publications
BACKGROUND: Hydroa vacciniforme (HV)-like lymphoma (HVL) is a rare and aggressive cutaneous T-cell lymphoma occurring mainly in children in Latin America and Asia. Chronic latent Epstein-Barr virus infection has been associated with both HV and HVL.
OBJECTIVE: We sought to evaluate the clinical presentation and histopathology of this rare cutaneous T-cell lymphoma.
METHODS: We reviewed the clinical, morphologic, and immunophenotypical features in 12 cases of HVL from Bolivia.
RESULTS: All 12 patients had skin lesions in both sun-exposed and nonsun-exposed areas, including edema, blistering, ulceration, and scarring, with a slowly progressive relapsing course. All 12 patients presented with systemic symptoms and showed a characteristic swelling of the nose and lips, and periorbital edema. Eight patients died an average of 5.3 months after initial diagnosis. Four patients remained alive with persistent disease. Histopathologic examination showed an atypical lymphocytic infiltrate with angiotropism and angiocentricity. The immunophenotype showed a cytotoxic T-cell (CD8(+)) profile. All cases were associated with Epstein-Barr virus infection and differed clinically from other forms of cutaneous T-cell lymphoma.
LIMITATIONS: Only a limited number of cases were studied.
CONCLUSIONS: This study confirms that HVL is a highly aggressive lymphoma, although some patients have a more indolent, chronic course.

Asai T, Tsuchiya Y, Okano K, et al.
Aflatoxin contamination of red chili pepper from Bolivia and Peru, countries with high gallbladder cancer incidence rates.
Asian Pac J Cancer Prev. 2012; 13(10):5167-70 [PubMed] Related Publications
Chilean red chili peppers contaminated with aflatoxins were reported in a previous study. If the development of gallbladder cancer (GBC) in Chile is associated with a high level of consumption of aflatoxin-contaminated red chili peppers, such peppers from other countries having a high GBC incidence rate may also be contaminated with aflatoxins. We aimed to determine whether this might be the case for red chili peppers from Bolivia and Peru. A total of 7 samples (3 from Bolivia, 4 from Peru) and 3 controls (2 from China, 1 from Japan) were evaluated. Aflatoxins were extracted with acetonitrile:water (9:1, v/v) and eluted through an immuno-affinity column. The concentrations of aflatoxins B1, B2, G1, and G2 were measured using high-performance liquid chromatography (HPLC), and then the detected aflatoxins were identified using HPLC-mass spectrometry. In some but not all of the samples from Bolivia and Peru, aflatoxin B1 or aflatoxins B1 and B2 were detected. In particular, aflatoxin B1 or total aflatoxin concentrations in a Bolivian samples were above the maximum levels for aflatoxins in spices proposed by the European Commission. Red chili peppers from Bolivia and Peru consumed by populations having high GBC incidence rates would appear to be contaminated with aflatoxins. These data suggest the possibility that a high level of consumption of aflatoxin-contaminated red chili peppers is related to the development of GBC, and the association between the two should be confirmed by a case-control study.

Stormo AR, Altamirano VC, Pérez-Castells M, et al.
Bolivian health providers' attitudes toward alternative technologies for cervical cancer prevention: a focus on visual inspection with acetic acid and cryotherapy.
J Womens Health (Larchmt). 2012; 21(8):801-8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Little is known about health providers' attitudes toward visual inspection with acetic acid (VIA) and cryotherapy in the prevention of cervical cancer, as most research in Latin America and the Caribbean (LAC) has examined attitudes of the general population. This study describes attitudes of Bolivian health professionals toward new technologies for cervical cancer prevention, focusing on VIA and cryotherapy.
METHODS: Between February 2011 and March 2012, we surveyed 7 nurses and 35 physicians who participated in 5-day workshops on VIA and cryotherapy conducted in Bolivia. Multiple choice and open-ended questions were used to assess participants' acceptability of these procedures and the feasibility of their implementation in the context of perceived barriers for the early detection of cervical cancer in this country.
RESULTS: Most believed that cultural factors represent the main barrier for the early detection of cervical cancer (70%), although all stated that VIA and cryotherapy would be accepted by women, citing the advantages of VIA over cytology for this belief. Most also believed their colleagues would accept VIA and cryotherapy (71%) and that VIA should replace Pap testing (61%), reiterating the advantages of VIA for these beliefs. Those who believed the contrary expressed a general resistance to change associated with an already existing cytology program and national norms prioritizing Pap testing.
CONCLUSIONS: Most participants had favorable attitudes toward VIA and cryotherapy; however, a sizable minority cited challenges to their adoption by colleagues and believed VIA should not replace cytology. This report can inform the development of strategies to expand the use of alternative cervical cancer screening methods in LAC and Bolivia.

Ladner J, Besson MH, Hampshire R, et al.
Assessment of eight HPV vaccination programs implemented in lowest income countries.
BMC Public Health. 2012; 12:370 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cervix cancer, preventable, continues to be the third most common cancer in women worldwide, especially in lowest income countries. Prophylactic HPV vaccination should help to reduce the morbidity and mortality associated with cervical cancer. The purpose of the study was to describe the results of and key concerns in eight HPV vaccination programs conducted in seven lowest income countries through the Gardasil Access Program (GAP).
METHODS: The GAP provides free HPV vaccine to organizations and institutions in lowest income countries. The HPV vaccination programs were entirely developed, implemented and managed by local institutions. Institutions submitted application forms with institution characteristics, target population, communication delivery strategies. After completion of the vaccination campaign (3 doses), institutions provided a final project report with data on doses administered and vaccination models. Two indicators were calculated, the program vaccination coverage and adherence. Qualitative data were also collected in the following areas: government and community involvement; communication, and sensitization; training and logistics resources, and challenges.
RESULTS: A total of eight programs were implemented in seven countries. The eight programs initially targeted a total of 87,580 girls, of which 76,983 received the full 3-dose vaccine course, with mean program vaccination coverage of 87.8%; the mean adherence between the first and third doses of vaccine was 90.9%. Three programs used school-based delivery models, 2 used health facility-based models, and 3 used mixed models that included schools and health facilities. Models that included school-based vaccination were most effective at reaching girls aged 9-13 years. Mixed models comprising school and health facility-based vaccination had better overall performance compared with models using just one of the methods. Increased rates of program coverage and adherence were positively correlated with the number of vaccination sites. Qualitative key insights from the school models showed a high level of coordination and logistics to facilitate vaccination administration, a lower risk of girls being lost to follow-up and vaccinations conducted within the academic year limit the number of girls lost to follow-up.
CONCLUSION: Mixed models that incorporate both schools and health facilities appear to be the most effective at delivering HPV vaccine. This study provides lessons for development of public health programs and policies as countries go forward in national decision-making for HPV vaccination.

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