A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HPV testing is more sensitive than cytology at identifying CIN2/3 lesions but with lower specificity.

“Studies, particularly in developed countries, suggest that HPV testing is more sensitive than cytology at identifying CIN 2=3 lesions but with lower specificity.10,[20][21][22][23][24][25]”

• cites [10] sourceSupported
• cites [20] sourceNot checked — no full text of the source
• cites [21] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Concerns have been expressed about the reproducibility and quality control of VIA in field conditions.

“Concerns have been expressed about the reproducibility and quality control of VIA in field conditions.18”

• cites [18] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

There is a gradual adoption of HPV testing in many developed as well as developing countries.

“Currently, there is interest in more widespread use of VIA in lowresource settings, 27 and there is a gradual adoption of HPV testing in many developed as well as developing countries.10”

• cites [10] sourceSupported

May combine two claims.

VIA has a higher sensitivity but lower specificity than cytology in developing countries.

“Reportedly, VIA has a higher sensitivity but lower specificity than that of cytology in developing countries.5,7”

• cites [5] sourceNot checked — no full text of the source
• cites [7] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

In a multicenter cross-sectional study in India, HPV testing had similar sensitivity to detect CIN2/3 lesions as cytology and VIA.

“In a multicenter cross-sectional study in India, HPV testing had similar sensitivity to detect CIN 2=3 lesions as cytology and VIA.26”

• cites [26] sourceSupported

May combine two claims.

In the first 10 months of screening, 13.3% of cytology smears were reported as LSIL and 6.0% as ASCUS.

“In the first 10 months of screening, 13.3% of cytology smears were reported as LSIL and 6.0% as ASCUS.”

May combine two claims.

Women diagnosed with invasive cancer during 2000-2003 included 112 (84 screen-detected and 28 clinically detected) in the VIA arm, 123 (81 screen-detected and 42 clinically detected) in the cytology arm, 91 (63 screen-detected and 28 clinically detected) in the HPV arm and 61 in the control group.

“Women diagnosed with invasive cancer during 2000-2003 included 112 (84 screen-detected and 28 clinically detected) in the VIA arm, 123 (81 screen-detected and 42 clinically detected) in the cytology arm, 91 (63 screen-detected and 28 clinically detected) in the HPV arm and 61 in the control group.”

May combine two claims.

While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing.

“While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing.”

May combine two claims.

Compliance with interview was similar between the 3 study arms (96.3% for VIA, 95.7% for cytology and 97.3% for HPV; p=0.09, Mann-Whitney test) but significantly lower in the control arm (93.5%; p=0.001, Mann-Whitney test).

“Compliance with interview was similar between the 3 study arms (96.3% for VIA, 95.7% for cytology and 97.3% for HPV; p 5 0.09, Mann-Whitney test) but significantly lower in the control arm (93.5%; p 5 0.001, Mann-Whitney test).”

May combine two claims.

Of the 38 women staged in the control group, 18% were in stage I and 58% in stage III.

“Of the 38 women staged, 18% were in stage I and 58% in stage III.”

May combine two claims.

The overall agreement between HPV testing in India and France was 92.0% with a kappa value of 0.86.

“The overall agreement (92.0%) had a j value of 0.86.”

May combine two claims.

Women in the control group were generally older (p=0.03, Mann-Whitney test) with a lower parity (p<0.001, Mann-Whitney test).

“Women in the control group were generally older (p 5 0.03, Mann-Whitney test) with a lower parity (p < 0.001, Mann-Whitney test).”

May combine two claims.

Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV.

“Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV.”

The quote only partly states this claim.

In the first training, interobserver agreement on VIA between the master trainer and the 9 test providers using 150 cervical photographs was 59.3% with a kappa value of 0.29 for classification into 3 categories.

“At the end of the first training, the interobserver agreement studies on VIA between the master trainer and the 9 test providers using 150 cervical photographs (69 negative, 67 positive and 14 invasive cancers) revealed an agreement rate of 59.3% and a j value of 0.29 (classification into 3 categories).”

May combine two claims.

After retraining, the ASCUS rate decreased to 2.1% and the LSIL rate to 1.4%.

“Following this, the ASCUS rate decreased to 2.1% and the LSIL rate to 1.4%; overall cytology positivity declined from 22% in the first year of screening to <5% in the remaining period without loss in case detection (Fig. 3b).”

May combine two claims.

The positive predictive value for detecting CIN 2=3 and invasive cancer was 7.5% (278=3,731) for VIA, 19.0% (340=1,790) for cytology and 10.9% (306=2,812) for HPV testing.

“The positive predictive value for detecting CIN 2=3 and invasive cancer was 7.5% (278=3,731) for VIA, 19.0% (340=1,790) for cytology and 10.9% (306=2,812) for HPV testing.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The characteristics of women who did not comply with diagnostic investigations were similar to the rest of those who had the diagnostic tests.

“The characteristics of women who did not comply with diagnostic investigations were similar to the rest of those who had the diagnostic tests.”

May combine two claims.

Overall, biopsies were carried out in 9.9% (n=2,643) of women screened in the VIA arm, 3.5% (n=905) in the cytology group and 4.3% (n=1,159) in the HPV group.

“Overall, biopsies were carried out in 9.9% (n 5 2,643) of women screened in the VIA arm, 3.5% (n 5 905) in the cytology group and 4.3% (n 5 1,159) in the HPV group.”

May combine two claims.

Rates of detection of CIN 2=3 and cancer were similar between arms (p=0.06 and p=0.16, respectively, Mann-Whitney test).

“Rates of detection of CIN 2=3 and cancer were similar between arms (p 5 0.06 and p 5 0.16, respectively, Mann-Whitney test)”

May combine two claims.

The overall distribution of cytology results was: inadequate 0.4%, normal 10.0%, inflammation 80.0%, HPV changes 2.9%, ASCUS 2.6%, LSIL 2.4%, HSIL 1.2%, and invasive cancer 0.4%.

“The overall distribution of cytology results was as follows: inadequate 111 (0.4%), normal 2,559 (10.0%), inflammation 20,436 (80.0%),HPV changes 740 (2.9%), ASCUS 662 (2.6%), LSIL 613 (2.4%), HSIL 306 (1.2%) and invasive cancer 108 (0.4%).”

May combine two claims.

The detection rate of condyloma=CIN1 was higher in the VIA arm (p<0.001, Mann-Whitney test), particularly for the younger women.

“but that of condyloma=CIN1 was higher in the VIA arm (p < 0.001, Mann-Whitney test), particularly for the younger women.”

May combine two claims.

Overall cytology positivity declined from 22% in the first year of screening to <5% in the remaining period without loss in case detection.

“Following this, the ASCUS rate decreased to 2.1% and the LSIL rate to 1.4%; overall cytology positivity declined from 22% in the first year of screening to <5% in the remaining period without loss in case detection (Fig. 3b).”

May combine two claims.

Overall, treatment was given to 80% of the women with CIN 1, 85% with CIN 2 and 88% with CIN 3.

“Overall, treatment was given to 80% of the women with CIN 1, 85% with CIN 2 and 88% with CIN 3.”

May combine two claims.

The most common form of treatment for invasive cancer in the intervention arm was radical hysterectomy (n=105, 46%), followed by radical radiotherapy.

“The most common form of treatment for invasive cancer in the intervention arm was radical hysterectomy (n 5 105, 46%), followed by radical radiotherapy.”

May combine two claims.

Detection rates obtained by HPV testing were similar to cytology, despite higher investments.

“Detection rates obtained by HPV testing were similar to cytology, despite higher investments.”

May combine two claims.

194 women were detected with CIN 2=3 lesions in the VIA arm, 259 in the cytology arm and 243 in the HPV arm.

“194 women were detected with CIN 2=3 lesions in the VIA arm, 259 in the cytology arm and 243 in the HPV arm.”

May combine two claims.

Of those tested in the control group, 15 were detected with histologically proved CIN 2=3 and 41 with invasive cancer.

“Of those tested, 15 were detected with histologically proved CIN 2=3 and 41 with invasive cancer.”

May combine two claims.

Cryotherapy was given to 55% of CIN 1 and 21% of CIN 2=3 cases; 25% of women with CIN 1 and 46% of women with CIN 2=3 had LEEP.

“Cryotherapy was given to 55% of CIN 1 and 21% of CIN 2=3 cases; 25% of women with CIN 1 and 46% of women with CIN 2=3 had LEEP.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A simple hysterectomy was carried out on 30% of women with CIN 3.

“A simple hysterectomy was carried out on 30% of women with CIN 3.”

May combine two claims.

Of 100 HPV samples retested in France, 8 cases positive in India had a negative result in France; 5 of these discordant samples had an RLU/PC ratio between 1.04 and 1.84 in India.

“Eight cases positive in India had a negative result in France; 5 of these discordant samples had an RLU=PC ratio between 1.04 and 1.84 in India.”

May combine two claims.

More than 80% of women with CIN2/3 had treatment, mostly with cryotherapy or LEEP.

“More than 80% of women with CIN 2=3 had treatment, mostly with cryotherapy or LEEP.”

May combine two claims.

Treatment rate of atypia/condyloma/CIN1 was 34.4% in the VIA arm, 46.1% in the cytology arm, and 30.7% in the HPV testing arm (p=0.002).

“Treatment rate of atypia=condyloma=CIN 1 (%) 34.4 17.9-52.7 46.1 23.1-66.7 30.7 15.6-45.7 0.002”

May combine two claims.

Detection rate of atypia/condyloma/CIN1 was 5.6% in the VIA arm, 2.0% in the cytology arm, and 2.3% in the HPV testing arm (p<0.001).

“Detection rate of atypia=condyloma=CIN 1 (%) 5.6 1.4-9.6 2.0 0.3-6.22.3 1.2-4.0<0.001”

May combine two claims.

Detection rate of CIN2/3 was 0.7% in the VIA arm, 1.0% in the cytology arm, and 0.9% in the HPV testing arm (p=0.06).

“Detection rate of CIN 2=3 (%) 0.7 0.3-1.5 1.0 0.6-1.6 0.9 0.6-1.40.06”

Probably not a substantial claim: may not pass S3 (load-bearing).

Hysterectomy was performed on one woman for severe bleeding after LEEP.

“No major side effects were documented following cryotherapy in our study; hysterectomy was performed on one woman for severe bleeding after LEEP.”

May combine two claims.

Compliance with colposcopy among screen-positive women was 98.5% in the VIA arm, 87.1% in the cytology arm, and 88.2% in the HPV testing arm (p<0.001).

“Compliance with colposcopy among screened positive (%) 98.5 96.0-99.7 87.1 79.5-91.888.2 79.3-94.4<0.001”

May combine two claims.

Treatment rate of CIN2/3 was 88.2% in the VIA arm, 88.3% in the cytology arm, and 83.3% in the HPV testing arm (p=0.22).

“Treatment rate of CIN 2=3 (%) 88.2 70.0-100.088.3 73.7-100.083.3 65.0-100.00.22”

May combine two claims.

Detection rate of cancer was 0.3% in the VIA arm, 0.3% in the cytology arm, and 0.2% in the HPV testing arm (p=0.16).

“Detection rate of cancer (%) 0.3 0.0-0.7 0.3 0.1-0.5 0.2 0.1-0.40.16”

May combine two claims.

Positivity rate among screened women was 14.0% in the VIA arm, 7.0% in the cytology arm, and 10.3% in the HPV testing arm.

“Positivity rate among screened (%) 14.0 8.5-19.6 7.0 3.7-16.1 10.3 8.6-12.4N=A”

Classified as probably not a substantial claim.

Cytology screening programs have resulted in a marked decline of cervical cancer in developed countries.

“Cytology screening programs have resulted in a marked decline of this disease in developed countries.2”

• cites [2]Not checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Cervical cancer is an important public health problem of adult women in many developing countries.

“Cervical cancer is an important public health problem of adult women in many developing countries.1,2”

• cites [1] sourceNot checked — no full text of the source
• cites [2]Not checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Osmanabad is a predominantly rural and socioeconomically backward district with a high incidence of cervical cancer (age-standardized rate 27.4 per 100,000 women).

“Osmanabad is a predominantly rural and socioeconomically backward district with a high incidence of cervical cancer (age-standardized rate 27.4=100,000 women).11”

• cites [11]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

The study was designed to have 80% power at the 5% significance level to detect a 50% reduction in cumulative mortality rate from cervical cancer within 15 years of enrollment between one of the arms and the control group.

“The study was designed to have 80% power at the 5% significance level to detect a 50% reduction in cumulative mortality rate from cervical cancer within 15 years of enrollment between one of the arms and the control group.”

May combine two claims.

VIA is a useful alternative but requires careful monitoring.

“VIA is a useful alternative but requires careful monitoring.”

• AssumptionRests on an assumption: VIA is simple and inexpensive and can be provided by midwives, nurses and other HWs.

Probably not a substantial claim: may not pass S3 (load-bearing).

All smears with positive cytology, all abnormal histology slides and a 10% random sample of negative smears and negative histology slides were reviewed by cytologists and pathologists from the TMC.

“All smears with positive cytology, all abnormal histology slides and a 10% random sample of negative smears and negative histology slides were reviewed by cytologists and pathologists from the TMC.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Screening was performed by 9 ANMs who were trained in the collection of cervical cell samples for cytology and HPV testing and in performing VIA and cryotherapy during a 3-week training course, using manuals prepared by the IARC.

“Screening was performed by 9 ANMs who were trained in the collection of cervical cell samples for cytology and HPV testing and in performing VIA and cryotherapy during a 3-week training course, using manuals prepared by the IARC.12,14”

• cites [12]Not checked — no full text of the source
• cites [14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

The most persuasive scientific evidence for the efficacy of a cancer screening test comes from RCTs with reduction in incidence of or mortality from the disease of interest as the end point.

“The most persuasive scientific evidence for the efficacy of a cancer screening test comes from RCTs with reduction in incidence of or mortality from the disease of interest as the end point.”

Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

The ultimate proof of efficacy of a screening test for cervical neoplasia is its ability to prevent invasive cancer when implemented in a program setting.

“The ultimate proof of efficacy of a screening test for cervical neoplasia is its ability to prevent invasive cancer when implemented in a program setting.”

Classified as probably not a substantial claim.

Since this trial used a cluster design, an appropriate analysis was carried out using the cluster as the unit of analysis.

“Since this trial used a cluster design, an appropriate analysis was carried out using the cluster as the unit of analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A random sample of 100 denatured cervical samples was retested in Grenoble for reproducibility of HC II results.

“A random sample of 100 denatured cervical samples was retested in Grenoble for reproducibility of HC II results.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study protocol was reviewed and approved by the institutional scientific and ethical review committees of the TMC=NDMCH and the IARC.

“The study protocol was reviewed and approved by the institutional scientific and ethical review committees of the TMC=NDMCH and the IARC.”

Classified as probably not a substantial claim.

Internal and external quality-control measures were introduced in the cytology, pathology and HPV laboratories.

“Internal and external quality-control measures were introduced in the cytology, pathology and HPV laboratories.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The mean parity of interviewed women differed significantly across the four study arms (p<0.001).

“Parity (number) 4.0 3.8-4.5 4.0 3.7-4.44.0 3.7-4.33.4 2.6-3.9 <0.001”

Probably not a substantial claim: may not pass S3 (load-bearing).

The mean age of interviewed women differed significantly across the four study arms (p=0.03).

“Age (years) 39.4 38.8-40.339.3 38.6-40.6 39.3 38.4-40.440.0 38.8-41.00.03”

May combine two claims.

A high level of participation and good-quality cytology can be achieved in low-resource settings.

“Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings.”

Classified as probably not a substantial claim.

The cluster randomization design was taken into account in the analysis.

“However, this design was taken into account in the analysis.”

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

Frequently repeated screening, although more effective, may not be feasible or may be too costly for implementation in most low-resource countries.

“Frequently repeated screening, although more effective, may not be feasible or may be too costly for implementation in most lowresource countries.3”

• cites [3]Not checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Data analysis was based on intention-to-treat; all women eligible in the clusters randomized were considered irrespective of their participation in the interview or the screening.

“Analysis was based on intention-to-treat; i.e., all women eligible in the clusters randomized were considered irrespective of their participation in the interview or the screening.”

May combine two claims.

HPV testing does not give any better detection of CIN2/3 lesions than cytology, despite higher investments.

“Our results clearly show that good-quality cytology can be implemented even in a rural setting of a developing country with reasonable investment, while HPV testing does not give any better detection of CIN 2=3 lesions, despite the higher investments.”

• AssumptionRests on an assumption: The currently available HPV test (HC II) is expensive and requires a relatively sophisticated laboratory infrastructure.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Higher detection rates reported for HPV testing in other studies may be due to poor-quality concurrent cytology.

“It is likely that higher detection rates reported for HPV testing in other studies may be due to poor-quality concurrent cytology.”

May combine two claims.

The different frequencies of inconclusive colposcopy may affect the detection rate of endocervical lesions but are unlikely to influence the detection of ectocervical lesions.

“The different frequencies of inconclusive colposcopy may affect the detection rate of endocervical lesions but are unlikely to influence the detection of ectocervical lesions.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Currently, there is interest in more widespread use of VIA in low-resource settings.

“Currently, there is interest in more widespread use of VIA in lowresource settings, 27 and there is a gradual adoption of HPV testing in many developed as well as developing countries.10”

• cites [27] sourceNot checked — no full text of the source