Table 2 Summary of Study Selection Criteria By Parameter Group

General criteria for stud y selection

• Nationally representative studies meeting selection criteria

   ➢ If unavailable, then select broad population-based studies

▪ If unavailable, then select local studies

• Specificity of results to HPV type groupings of interest (16/18 or 6/11)

   ➢ If studies specific to HPV 16/18 or 6/11 infection or disease are unavailable, then select studies of all high-risk or all low-risk HPV types, respectively

▪ If unavailable then select studies for all infections or disease

• PCR-based methods for HPV detection in infections

Progression of HPV infection and disease

• Histologic confirmation of cervical disease

• Data available for outcomes reported over a 12-month time horizon

HPV infection mean duration in absence of detectable disease

• Specificity of results to HPV type groupings of interest (16/18 or 6/11)

• Truncation of infection duration at time of disease detection via histology

• Limited degree of censoring beyond longest infection follow-up time

Regression of HPV infection and disease

• Histologic confirmation of cervical disease at baseline

• Biopsy confirmation of cervical HPV-type specific disease absence during follow-up to connote regression

   ➢ If unavailable for all cases, then select studies with either biopsy confirmed HPV-type specific disease absence for a portion of cases, with negative cytology for non-biopsied cases, OR biopsy confirmed disease absence, irrespective of HPV-type

• Data available for outcomes reported over a 12-month time horizon

Cervical cancer mortality

• Data available on an age- and stage-specific basis

• Nationally representative or broad population-based studies in unscreened women

   ➢ If unavailable, then select nationally representative or broad population-based studies in screened and unscreened women

• Data available for outcomes reported over a 12-month time horizon

Hysterectomy for non-HPV related conditions

• Age-specific annual hysterectomy rates reported

Cytology screening rates

• Age-specific annual routine cervical cytology screening rates reported

   ➢ Routine screening reported separately from follow-up screening

   ➢ Cervical cytology reported separately from vaginal cytology

• Data based on documented screening utilization in a population-based study if available

   ➢ If unavailable, then select studies based on patient self-report

Cytology sensitivity

• Liquid-based cytology evaluated

• Cervical biopsy performed on all women

   ➢ If unavailable, then select studies in which cervical biopsy was performed on at least a random sample of women with negative cytology and colposcopy results

Cytology specificity

• Liquid-based cytology evaluated

• Cervical colposcopy performed on all women, with biopsy performed if abnormalities suspected

• Biopsy results reported for all grades of cervical disease (≥ CIN 1)

Colposcopy sensitivity/specificity

• Colposcopy performed following abnormal cytology

• Colposcopically directed cervical biopsy performed on all women

• Biopsy results reported for all grades of cervical disease (≥ CIN 1)

Symptom development among cancer patients

• Stage-specific symptom development

• Representative cross-section of patients with cervical cancer at each stage including patients who may harbor occult cancers

   ➢ If unavailable, then rely upon expert opinion from the literature

Eradication of CIN with treatment

• Representative study of CIN therapies used in practice if available

   ➢ If unavailable then select studies of LEEP (most common modality)

• Stratified reporting of outcomes by pre-treatment CIN grade

• Post-treatment follow-up of all women within 12 months via colposcopy and/or biopsy

• Definition of recurrent or residual disease as CIN 1 or more severe histology

Eradication of cervical cancer with treatment

• Nationally representative or broad population-based studies of 5-year disease-free survival by cancer stage

   ➢ If unavailable, then select nationally representative or broad population-based studies of 5-year relative survival by cancer stage

Eradication of genital warts with treatment

• Representative study of genital wart treatments used in clinical practice

• Physician ascertained clearance following treatment for all subjects

Persistence of HPV following cervical disease eradication

• Representative study of therapies used in practice if available

   ➢ If unavailable, then select studies of LEEP (most common modality) for CIN, and hysterectomy or radiation therapy for cervical cancer

• Histologic confirmation of disease pre-treatment and post-treatment (for exclusionary study purposes)

• HPV typing of pre- or post-treatment lesion tissue specimens or both

   ➢ If unavailable, then select studies with HPV typing of any cervical specimen

• Follow-up for all women within 6 months post-treatment

   ➢ If unavailable, then select studies with less prompt follow-up

• Colposcopy performed on all women post-treatment to assist in confirming disease eradication

Persistence of HPV following genital wart eradication

• Representative study of genital wart treatments used in clinical practice

• Testing for HPV infection across a range of anogenital sites post-treatment (not just at the former wart site)

• Follow-up for all women within 6 months post-treatment

   ➢ If unavailable, then select studies with less prompt follow-up

Care seeking behavior for genital warts

• Population-based studies of patients with genital warts, including both those who have, and who have not, chosen to seek physician care

   ➢ If unavailable, then rely upon expert opinion from the literature