US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines

Abstract

Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines.

Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination.

Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups.

Conclusions: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.

Figure 1.

Flow chart of selected cases from all cancer tissues, Centers for Disease Control and Prevention Cancer Registry Sentinel Surveillance System for human papillomavirus (HPV) typing of cancers. All samples were tested by Linear Array HPV genotyping test (LA), but if the results were inadequate or negative INNO-LiPA HPV genotyping (LiPA) was performed. If LiPA detected HPV, then the HPV results were based on the LiPA test.

Figure 2.

Human papillomavirus (HPV) detection by cancer site. The percent HPV-positive cancers was determined using all cancers for that anatomic site as denominator. Ninety-five percent Wilson confidence limits around the prevalence estimates are presented. These percentages reflect the HPV DNA that was detected. Finding HPV in a cancer tissue does not necessarily indicate a causal relationship. International Agency for Research on Cancer defined some cancers to have strong evidence for causal etiology such as cervical, vaginal, vulvar, anal, penile, and oropharyngeal cancers. Oral cavity and laryngeal cancers are considered to have less evidence for causal etiology (larynx) and/or inconsistent correlation with HPV DNA detection and percent causal (oral cavity and larynx). Cancer sites were determined using the following ICD-O-3 morphology codes: C53 (cervix), C51 (vulva), C52 (vagina), C21 (anus), C60 (penis), and C01.9, C02.4, C02.8, C05.1, C05.2, C05.9, C09.0, C09.1, C09.8, C09.9, C10.0, C10.2, C10.8, C10.9, C14.0, C14.2, and C14.8 (oropharynx), C02.0, C02.1, C02.2, C02.3 C02.9, C03.0, C03.1, C03.9, C04.0, C04.1, C04.8, C04.9, C05.0, C06.0, C06.1, C06.2, C06.8, C06.9 (oral tongue and oral cavity), C32.0, C32.1, C32.2, C32.3, C32.8, C32.9 (larynx). ICD-O-3 morphology codes: 9590–9729, 9827 (lymphoma), 8800–8991 (sarcoma), and 8720–8790 (melanoma) were not included.

Figure 3.

The seven most common oncogenic human papillomavirus (HPV) genotypes detected in select anogenital and head and neck cancers. A) Anogenital cancers incude cervical, vaginal, vulvar, anal, and penile cancers. B) Head and neck cancers include oropharyngeal, laryngeal, and oral cavity cancers. Number of types may add up to more than seven in instances where we found ties in the percentages.

Figure 3.

The seven most common oncogenic human papillomavirus (HPV) genotypes detected in select anogenital and head and neck cancers. A) Anogenital cancers incude cervical, vaginal, vulvar, anal, and penile cancers. B) Head and neck cancers include oropharyngeal, laryngeal, and oral cavity cancers. Number of types may add up to more than seven in instances where we found ties in the percentages.

Figure 4.

Population attribution of human papillomavirus (HPV) in select anogenital and head and neck cancers. A) Anogenital cancers include cervical, vaginal, vulvar, anal, and penile cancers. It should be noted that the International Agency for Research on Cancer (IARC) has defined some cancers to have strong evidence for a causal association of HPV 16 and 18 with cervical, vaginal, vulvar, anal, and penile. Percent multiple infections ranged by type of anogenital cancer: cervical 8.2%; in situ cervical 21.4%; vulvar 6.3%, in situ vulvar 7.4%, vaginal 15%, anal 11.0%, penile 11.4%. Ninety-five percent Wilson confidence limits around the prevalence estimates are presented. B) Select head and neck cancers include oropharyngeal (OP), laryngeal, and oral cavity (OC) cancers. According to IARC, there is strong evidence for a causal role of HPV 16 and 18 in oropharyngeal cancer. The oral cavity is considered to have evidence for a causal association with HPV, but some of the HPV DNA detected in tissues may not represent the true causal agent. Laryngeal cancer has limited evidence for a causal etiology with HPV; and the correlation of HPV DNA detected does not reflect the percentage that is causal. C) Percent multiple infections were similar across cancer types for OP, OC, and laryngeal cancers (4.1%). Ninety-five percent Wilson confidence limits around the prevalence estimates are presented.

Figure 4.

Population attribution of human papillomavirus (HPV) in select anogenital and head and neck cancers. A) Anogenital cancers include cervical, vaginal, vulvar, anal, and penile cancers. It should be noted that the International Agency for Research on Cancer (IARC) has defined some cancers to have strong evidence for a causal association of HPV 16 and 18 with cervical, vaginal, vulvar, anal, and penile. Percent multiple infections ranged by type of anogenital cancer: cervical 8.2%; in situ cervical 21.4%; vulvar 6.3%, in situ vulvar 7.4%, vaginal 15%, anal 11.0%, penile 11.4%. Ninety-five percent Wilson confidence limits around the prevalence estimates are presented. B) Select head and neck cancers include oropharyngeal (OP), laryngeal, and oral cavity (OC) cancers. According to IARC, there is strong evidence for a causal role of HPV 16 and 18 in oropharyngeal cancer. The oral cavity is considered to have evidence for a causal association with HPV, but some of the HPV DNA detected in tissues may not represent the true causal agent. Laryngeal cancer has limited evidence for a causal etiology with HPV; and the correlation of HPV DNA detected does not reflect the percentage that is causal. C) Percent multiple infections were similar across cancer types for OP, OC, and laryngeal cancers (4.1%). Ninety-five percent Wilson confidence limits around the prevalence estimates are presented.