Disusun Oleh

ARIE HENDRIYANA
10/309220/PKU/12023
PROGRAM PASCASARJANA
MINAT MANAJEMEN KEBIJAKAN OBAT
ILMU KESEHATAN MASYARAKAT
FAKULTAS KEDOKTERAN
UNIVERSITAS GADJAH MADA
2011

A. Please read the Case–Control Study of Human Papillomavirus and Oropharyngeal

Cancer G. D’Souza and Others - 10 May, 2007 in the New England Journal of medicine.
This article can be downloaded from the following address:
http://content.nejm.org/cgi/reprint/356/19/1944.pdf. The investigators were looking for
associations between HPV and oropharyngeal cancer. Use the table 3 to answer questions
1-5.
1. In Table 3:
a) There is no association between having Positive Oral HPV-16 infection and
oropharyngeal cancer because the confidence interval does not cross 1.0.
Jawab:Salah
Yang benar adalah ada hubungan yang signifikan (OR 14.6 ; CI 95%(6.3–36.6).

b) There is a 33.3-fold increase in oropharyngeal cancer in patients seropositive for E6

or E7 but it is not statistically significant.
Jawab: salah
Yang benar adalah peningkatan 58,4 kali lipat pada kanker orofaringeal.

c) There is a 32.2-fold adjusted increase in the odds of oropharyngeal cancer for those
with Seropositive HPV-16 L1 serologic status and it is statistically significant.
Jawab: Benar
karena OR 32,2 dengan CI 95% (14,6-71,3).

d) The data cannot be interpreted because the numbers are too sparse.
Jawab: Salah
 e) According to these data, patient who were seropositive for HPV-16 L1 were less
likely to develop oropharyngeal cancer.
Jawab: Salah

2. Calculate the unadjusted risk ratio for the risk of oropharyngeal cancer in patients
who were positive for oral HPV-16 infection.
a) 17.6
b) 11.4
c) 3.06
d) 8.0
e) Cannot calculate from the information given.
3. What statistical method was used to calculate the ―adjusted odds ratios‖ givenin the
table?
a) Linear regression (continues outcome) contoh: berat badan.
b) Cox regression (time-to-event outcomes) contoh: time to death
a) Poisson regression
b) Logistic regressionbenar (binary outcome)
c) Multiple 2x2 tables

4. The unadjusted odds ratio for HPV-16 L1 seropositivity is 17.6 but the adjusted odds
ratio is 32.2. How do you explain this difference?
a. This is most likely an error as adjustment for confounding should always reduce
the magnitude of the odds ratio.
Jawab:
Benar
b. The change is irrelevant since both odds ratios are statistically significant anyway.
c. The unadjusted odds ratio was an underestimate—which could happen if some of
the confounders were inversely related to exposure or disease.
d. Since both odds ratios are statistically significant, this indicates that there is little
confounding going on.
e. The unadjusted odds ratio was artificially inflated due to confounding.
5. Which of the following represents the correct statistic for comparing oral HPVinfection
prevalence in cases versus controls?
B. The following figure displays the Hazards Ratios derived from five different Cox
regression models. Use the table 4 from the article in the NEJM available in the web as
follow: http://content.nejm.org/cgi/reprint/356/11/1099.pdf. Please answer questions 1-4
belows.
1. Which of the following is the result of an unadjusted (univariate) analysis?
a) Female sex.
b) 1.039 (1.012-1.066)
c) 1.023 (0.997-1.049)
d) None of the above. Since this is a Cox-Regression, it is always an
adjusted(multivariate) analysis .Jawaban: Benar

2. Weekend admission is a statistically significant predictor of death in all thefollowing

except? Model 1 (column 1)
a) Model 2 (column 2)
b) Model 3 (column 3)
c) Model 4 (column 4)
d) Model 5 (column 5). jawaban: benar1.023 (0.997–1.049) terdapat nilai 1 dalam
nilai intervalnya, sehingga tidak signifikan.

3. According to the statistical modeling performed by the authors, which of thefollowing

variable groups may be explaining the increased risk of death amongpatients admitted on
the weekends for treatment of M.I.?
a) Age of patient and female sex.
b) Mechanical and arrhythmic complications.
c) Longer length of stay when patients are admitted on the weekend.
d) No invasive cardiac procedure within 30 days of admission.
Jawaban: benar OR 1.715 CI 95% (1.632–1.802)

4. Which of the following pair reflects the 1) PRIMARY INDEPENDENT VARIABLE

of interest AND the 2) DEPENDENT VARIABLE in this table of Cox
RegressionModels..
a) Primary Indep: Weekend Admission. Depend Variable: Cardiac
InterventionProcedures (including catheterization, PCI, and CABG).
 b) Primary Indep: Cardiac Intervention Procedures (including catheterization,PCI, and
CABG). Depend Variable: Time to Death.
c) Primary Indep: Weekend Admission. Depend Variable: Time to Death.\
Jawaban: benar
d) Primary Indep: Age. Depend Variable: Time to Death.

C. The following figure displays the Kaplan-Meier curves from a randomized trialcomparing
botulism toxin A with botulism toxin B for the treatment of cervicaldystonia (n=122).
Patients were followed until their pain returned or until theywere censored.

Bahan bacaan:
Cox proportional hazards assumes that thehazard ratio is constant at all time points.
That is to say, if patients in atrial fibrillationhave a risk of stroke that is twice as high
aspatients in sinus rhythm at one time point,then the risk in patients with atrial
fibrillationremains roughly twice as high at all othertimes. If this assumption does not
hold, thenCox proportional hazards analysis should notbe used. This can be assessed using
a Kaplan-Meier curve as in figure 4. In these plots, theprobability of surviving at each time
point iscalculated conditional on having survived upto that time point, which uses the data
at thetime point of interest, and all previous timepoints. As patients die or are lost to
followup,they cease to add further information to
the calculations at later time points. Thismeans that as patients have events or dropout of
the study, there is more uncertainty
1. Which of the following can be concluded directly from the figure?
Figure 1: The Kaplan-Meier curves from a randomized trial comparing botulism toxin
Awith botulism toxin B for the treatment of cervical dystonia.
(a) Botulism toxin A is a better drug for treating cervical dystonia than toxin B.\
(b) Botulism toxin B is a better drug for treating cervical dystonia than toxin A.
(c) The median time to return of pain was longer in the botulism toxin A groupthan
the B group.
(d) The median time to return of pain was longer in the botulism toxin B groupthan
the A group.
(e) There is a statistically significant difference between the treatments.
Jawaban: benar
2. The authors also ran a univariate Cox regression to get the hazard ratio
comparingtreatment A to treatment B for the outcome return of pain. The hazard ratio
from this model will be:
(a) =1.0
(b) > 1.0jawaban: benar
(c) < 1.0
(d) ≥1.0
(e) ≤1.0
3. The median time to return of pain in the botulism toxin A group was
approximately:
(a) 0 weeks
(b) 5 weeks
(c) 12 weeks
(d) 14 weeksjawaban:benar
(e) 25 weeks

4. The estimate of survival from pain for the botulism toxin A group at 19 weeks is
About.
(a) 100%
(b) 80%
(c) 70%
(d) 50%
(e) 30%jawaban: benar
1. In a linear regression model, a good ruleof thumb is that there should be at least10
patients for every variable selected.
2. In a logistic regression model, thereshould be at least 10 patients with theless common
of the two possible outcomesfor every variable included in themodel—that is, in a
data set in which 80patients did not have strokes, and 20 did,you can include two
variables in a logisticregression model to predict stroke (forexample, age and blood
pressure).
3. In Cox proportional hazards, you shouldhave at least 10 outcome events (forexample,
death) per explanatory variablethat you include.

Penjelasan tabel 3:
Oropharyngeal cancer was also strongly associated with serologic measures of exposure
to HPV-16 and with the presence of oral HPV infection (Table 3). Oropharyngeal cancer
was significantly associated with seropositivity for the HPV-16 L1 capsid protein, a
validated measure of lifetime HPV-16 exposure (odds ratio, 32.2; 95% CI, 14.6 to 71.3).
The presence of an oral HPV-16 infection was strongly associated with oropharyngeal
cancer (odds ratio, 14.6; 95% CI, 6.3 to 36.6), as was oral infection with any of 37 HPV
types (odds ratio, 12.3; 95% CI, 5.4 to 26.4) (Table 3).

Background
Substantial molecular evidence suggests a role for human papillomavirus (HPV) in
the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data
have been inconsistent.
Methods
We performed a hospital-based, case–control study of 100 patients with newly diagnosed
oropharyngeal cancer and 200 control patients without cancer to evaluate associations
between HPV infection and oropharyngeal cancer. Multivariate logisticregression models
were used for case–control comparisons.

Results
A high lifetime number of vaginal-sex partners (26 or more) was associated with
oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was
a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI,
1.3 to 8.8). The degree of association increased with the number of vaginal-sex and
oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal
cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds
ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio,
12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds
ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81)
of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were
seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity
was highly associated with oropharyngeal cancer among subjects with a history of
heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among
those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association
was similarly increased among subjects with oral HPV-16 infection, regardless of
their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the
association with oropharyngeal cancer primarily among subjects without exposure
to HPV-16.
Conclusions
Oral HPV infection is strongly associated with oropharyngeal cancer among subjects
with or without the established risk factors of tobacco and alcohol use.