Moving Forward: Human Papillomavirus Vaccination and the Prevention of Cervical Cancer

Abstract

In June 2006, the Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) vaccine. The vaccine was subsequently recommended by the Centers for Disease Control and Prevention's (CDC) Advisory Committee for Immunization Practices (ACIP) for routine vaccination of 11-12-year-old girls and catch-up vaccination of females 13-26 years of age. With the approval of the first HPV vaccine, cervical cancer now has a primary prevention tool. However, the availability of an HPV vaccine will not change the course of cervical cancer in this country unless there is both widespread demand by and access for the targeted populations. Demand will require recognition of the need for protection against HPV infection as well as a positive perception of the vaccine as safe and efficacious. General knowledge of HPV and its relationship to cervical cancer is limited; some parents and healthcare providers are hesitant to vaccinate preadolescent girls. Access to the expensive vaccine will not be increased without addressing financial constraints. Although the Vaccines for Children (VFC) program has added HPV to its vaccine plan, not all private insurers have approved coverage, and the uninsured and underinsured may have limited access. Moving forward will require a well-planned and executed public information campaign by trusted sources and the development of a comprehensive vaccine administration program. Although mandates would assure the broadest coverage, controversies surrounding mandates may deter work toward broad coverage. States should focus on developing a comprehensive program and then return to the mandate issue if coverage does not meet public health objectives.

A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers

“…Cells were pulsed with 10 M HLA-A*0201-restricted HPV-16 peptides or with 10 M HLA-A*0201-restricted HTLV-TAX [11][12][13][14][15][16][17][18][19] (LLFGYPVYV)-positive control peptide and 5 g/ml ␤2-microglobulin (BD Biosciences) for 6 h at 37°C in serum-free AIM V media (Invitrogen). HLA-A*0201 expression was determined by flow cytometry (FACSAria) using FITC-conjugated BB7.2 mAb (BD Biosciences).…”

“…In the first step one measures a solution with known target and calibrant concentrations to relate the MS 3 ion flux of the target to the calibrant in the detection spectra. For example, to quantitate E7 [11][12][13][14][15][16][17][18][19] , known amounts of this and a control peptide P (KSPWFTTK) are added to a mock MHC I workup using 1.2 pmol of ␤-galactosidase digest as a carrier. After C18 trapping and elution into the electrospray buffer, the detection MS 3 spectra of both peptides is taken in an alternating series to compensate for time variation in the nanospray ion flux.…”

“…After C18 trapping and elution into the electrospray buffer, the detection MS 3 spectra of both peptides is taken in an alternating series to compensate for time variation in the nanospray ion flux. The MS 3 signal amplitudes of P (base peak at m/z 597.4) and E7 [11][12][13][14][15][16][17][18][19] (base peak at m/z 634.4), corrected for relative amounts, are recorded. As noted in Fig.…”

“…In the second step a known amount of the calibrant peptide is added to the sample being quantitatively analyzed for target. For E7 [11][12][13][14][15][16][17][18][19] quantitation in 10 million CaSki cells, 40 fmol of KSPWFTTK is added to the sample at the beginning of the acid elution step. The detection MS 3 spectra of peptide P and E7 [11][12][13][14][15][16][17][18][19] is again taken in alternating sequence.…”

“…Among E6 and E7 proteins, only a single 9-mer epitope was found on all HPV-16 transformants tested. This conserved peptide, termed E7 [11][12][13][14][15][16][17][18][19] , is predicted to have the capacity to bind to the vast majority of globally distributed A2 alleles (100 of 116 HLA-A2 alleles). We suggest that the lack of prior clinical effectiveness of targeted CTL epitope vaccination (32) is a consequence of misidentification of peptides displayed on tumor cells because of the use of indirect immunological surrogates (killing, proliferation, cytokine production, etc.)…”